Purchasability


Ligand source activities (1 row/activity)

Select all ChEMBL ID Receptor Species Purchasable p-value
(-log)
Activity
Type
Activity
Relation
Activity
Value
Unit Assay Type Assay Description Mol
weight
Rot
Bonds
H don H acc LogP Smiles
CHEMBL216981 cxcr2_human Human Yes 10.3 IC50 = 0.0 nM Bind
Binding affinity to CXCR2Binding affinity to CXCR2
397 7 3 7 2.9 CC[C@H](c1ccc(o1)C)NC1=C(C(=O)C1=O)Nc1cccc(c1O)C(=O)N(C)C
CHEMBL189475 cxcr2_human Human Yes 10.0 IC50 = 0.1 nM Bind
Inhibition of CXCR2 (unknown origin)Inhibition of CXCR2 (unknown origin)
375 5 1 6 1.1 C[C@@H](C(=O)NS(C)(=O)=O)c1ccc(OS(=O)(=O)C(F)(F)F)cc1
CHEMBL4442431 cxcr2_human Human Yes 10.0 IC50 = 0.1 nM Bind
Inhibition of CXCR2 (unknown origin)Inhibition of CXCR2 (unknown origin)
375 5 1 6 1.1 C[C@@H](C(=O)NS(C)(=O)=O)c1ccc(OS(=O)(=O)C(F)(F)F)cc1
CHEMBL4462143 cxcr2_mouse Mouse No 10.0 IC50 = 0.1 nM Bind
Inhibition of CXCR2-mediated chemotaxis in mouse BAF3 cellsInhibition of CXCR2-mediated chemotaxis in mouse BAF3 cells
478 7 3 8 3.1 CC[C@@H](Nc1c(Nc2cccc(C(=O)N3CCN4CCC[C@H]4C3)c2O)c(=O)c1=O)c1ccc(C)o1
CHEMBL577075 cxcr2_human Human No 9.9 IC50 = 0.1 nM Bind
Antagonist activity at CXCR2 (unknown origin)Antagonist activity at CXCR2 (unknown origin)
346 7 3 7 1.1 CCN(CC)Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O
CHEMBL4066904 cxcr2_human Human No 9.8 IC50 = 0.2 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
445 5 3 5 4.0 CC1=CCC[C@H]1NC(=O)Nc1ccc(C#N)c(S(=O)(=O)C(C)(C)CC(F)(F)F)c1O
CHEMBL4082136 cxcr2_human Human No 9.7 IC50 = 0.2 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
377 3 3 5 3.1 CC1=CCC[C@H]1NC(=O)Nc1ccc(C#N)c(S(=O)(=O)C(C)(C)C)c1O
CHEMBL4098864 cxcr2_human Human No 9.7 IC50 = 0.2 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
432 4 3 5 3.5 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2(F)CCOCC2)c1O
CHEMBL4128926 cxcr2_human Human No 9.6 IC50 = 0.2 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor after 60 mins by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor after 60 mins by scintillation counting analysis
583 8 3 6 5.8 CC(C)(C)NS(=O)(=O)c1ccc(-c2sc(C(=O)N[C@H]3C[C@H](C(=O)O)C3)nc2CC2CCCCC2)c2ccccc12
CHEMBL4060139 cxcr2_human Human No 9.6 IC50 = 0.3 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
436 6 4 5 3.4 CC(C)(CCO)S(=O)(=O)c1c(Cl)ccc(NC(=O)N[C@@H]2CCC=C2Cl)c1O
CHEMBL4062361 cxcr2_human Human No 9.6 IC50 = 0.3 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
428 5 3 5 3.5 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)(C)C2COC2)c1O
CHEMBL4072270 cxcr2_human Human No 9.6 IC50 = 0.3 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
414 4 4 5 3.0 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)[C@@H]2CC[C@@H](O)C2)c1O
CHEMBL4077201 cxcr2_human Human No 9.5 IC50 = 0.3 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
442 5 3 5 4.0 CCC1(S(=O)(=O)c2c(Cl)ccc(NC(=O)N[C@@H]3CCC=C3C)c2O)CCOCC1
CHEMBL3818853 cxcr2_human Human No 9.5 IC50 = 0.3 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
446 4 3 4 5.2 O=C(Nc1ccc(Cl)c(S(=O)(=O)C2CCCC2)c1O)Nc1cccc(F)c1Cl
CHEMBL3818984 cxcr2_human Human No 9.5 IC50 = 0.3 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
432 4 3 4 4.8 O=C(Nc1ccc(Cl)c(S(=O)(=O)C2CCC2)c1O)Nc1cccc(F)c1Cl
CHEMBL3819480 cxcr2_human Human No 9.5 IC50 = 0.3 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
460 4 3 4 5.6 O=C(Nc1ccc(Cl)c(S(=O)(=O)C2CCCCC2)c1O)Nc1cccc(F)c1Cl
CHEMBL3817901 cxcr2_human Human No 9.4 IC50 = 0.4 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
420 4 3 4 4.7 CC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)Nc2cccc(F)c2Cl)c1O
CHEMBL4066818 cxcr2_human Human No 9.4 IC50 = 0.4 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
372 4 3 4 3.5 CC1=CCCC1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)C)c1O
CHEMBL4070506 cxcr2_human Human No 9.4 IC50 = 0.4 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
467 5 3 5 4.1 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2CCN(C3CCC3)CC2)c1O
CHEMBL4086957 cxcr2_human Human No 9.4 IC50 = 0.4 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
394 4 3 4 3.7 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)(F)F)c1O
CHEMBL3818581 cxcr2_human Human No 9.4 IC50 = 0.4 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
543 4 3 5 5.9 CN1CCC2(CCC(S(=O)(=O)c3c(Cl)ccc(NC(=O)Nc4cccc(F)c4Cl)c3O)CC2)CC1
CHEMBL3819163 cxcr2_human Human No 9.4 IC50 = 0.4 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
487 4 3 5 4.4 CN1CC2(CC(S(=O)(=O)c3c(Cl)ccc(NC(=O)Nc4cccc(F)c4Cl)c3O)C2)C1
CHEMBL4066510 cxcr2_human Human No 9.3 IC50 = 0.5 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
428 4 3 5 3.6 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2(C)CCOCC2)c1O
CHEMBL4082031 cxcr2_human Human No 9.3 IC50 = 0.5 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
452 4 3 5 3.7 O=C(Nc1ccc(Cl)c(S(=O)(=O)C2(F)CCOCC2)c1O)N[C@@H]1CCC=C1Cl
CHEMBL4088551 cxcr2_human Human No 9.3 IC50 = 0.5 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
456 5 3 5 4.3 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)(C)C2CCOCC2)c1O
CHEMBL4103349 cxcr2_human Human No 9.3 IC50 = 0.5 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
440 4 3 4 4.4 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)(C)C(F)(F)F)c1O
CHEMBL3817901 cxcr2_human Human No 9.3 IC50 = 0.5 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
420 4 3 4 4.7 CC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)Nc2cccc(F)c2Cl)c1O
CHEMBL3818277 cxcr2_human Human No 9.3 IC50 = 0.5 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
461 4 3 5 4.0 CN1CC[C@H](S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c2O)C1
CHEMBL3818793 cxcr2_human Human No 9.3 IC50 = 0.5 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
464 4 3 5 4.6 O=C(Nc1ccc(Cl)c(S(=O)(=O)C2CCOC2)c1O)Nc1cccc(Cl)c1Cl
CHEMBL3818827 cxcr2_human Human No 9.3 IC50 = 0.5 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
489 4 3 5 4.7 CN1CCC[C@H](S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c2O)CC1
CHEMBL3819221 cxcr2_human Human No 9.3 IC50 = 0.5 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
425 3 3 3 5.1 O=C(Nc1ccc(Cl)c(C(=O)N2CCCCC2)c1O)Nc1cccc(F)c1Cl
CHEMBL3819295 cxcr2_human Human No 9.3 IC50 = 0.5 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
422 4 3 4 4.8 CCS(=O)(=O)c1c(Cl)ccc(NC(=O)Nc2cccc(Cl)c2Cl)c1O
CHEMBL3819512 cxcr2_human Human Yes 9.3 IC50 = 0.5 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
475 4 3 5 4.4 CN1CCC(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c2O)CC1
CHEMBL3819569 cxcr2_human Human No 9.3 IC50 = 0.5 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
434 3 3 4 5.1 CC(C)(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)Nc2cccc(F)c2Cl)c1O
CHEMBL4079102 cxcr2_human Human No 9.2 IC50 = 0.6 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
404 5 3 4 3.8 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)(C)CF)c1O
CHEMBL4098979 cxcr2_human Human No 9.2 IC50 = 0.6 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
459 6 3 5 3.5 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2CCN(CCF)CC2)c1O
CHEMBL3818216 cxcr2_human Human No 9.2 IC50 = 0.6 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
436 4 3 4 5.2 CC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)Nc2cccc(Cl)c2Cl)c1O
CHEMBL3818458 cxcr2_human Human No 9.2 IC50 = 0.6 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
478 4 4 5 3.6 O=C(Nc1ccc(Cl)c(S(=O)(=O)N2CCNCC2)c1O)Nc1cccc(Cl)c1Cl
CHEMBL4089421 cxcr2_human Human No 9.1 IC50 = 0.8 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
418 4 3 5 3.1 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2(F)CCOC2)c1O
CHEMBL3818820 cxcr2_human Human No 9.1 IC50 = 0.8 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
478 4 3 5 4.9 O=C(Nc1ccc(Cl)c(S(=O)(=O)C2CCOCC2)c1O)Nc1cccc(Cl)c1Cl
CHEMBL3818917 cxcr2_human Human No 9.1 IC50 = 0.8 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
476 4 3 5 3.4 CN1CCN(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c2O)CC1
CHEMBL3819542 cxcr2_human Human No 9.1 IC50 = 0.8 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
492 4 3 5 3.9 CN1CCN(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(Cl)c3Cl)c2O)CC1
CHEMBL191413 cxcr2_human Human Yes 9.0 IC50 = 1 nM Funct
Antagonist activity at CXCR2 assessed as inhibition of CXCL8-induced neutrophil chemotaxisAntagonist activity at CXCR2 assessed as inhibition of CXCL8-induced neutrophil chemotaxis
283 5 1 3 2.1 CC(Cc1ccc(cc1)[C@H](C(=O)NS(=O)(=O)C)C)C
CHEMBL4067429 cxcr2_human Human Yes 9.0 IC50 = 1 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
414 4 3 5 3.2 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)[C@@]2(C)CCOC2)c1O
CHEMBL4076053 cxcr2_human Human No 9.0 IC50 = 1 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
426 4 3 5 3.2 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2CC3(COC3)C2)c1O
CHEMBL4076428 cxcr2_human Human No 9.0 IC50 = 1 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
453 5 3 5 3.7 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)[C@H]2C[C@H](N3CCCC3)C2)c1O
CHEMBL4094324 cxcr2_human Human No 9.0 IC50 = 1 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
392 4 3 4 3.6 CC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)NC2CCC=C2Cl)c1O
CHEMBL4095602 cxcr2_human Human No 9.0 IC50 = 1 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
386 3 3 4 3.8 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)(C)C)c1O
CHEMBL4097602 cxcr2_human Human No 9.0 IC50 = 1 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
427 5 3 5 3.1 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)[C@H]2C[C@H](N(C)C)C2)c1O
CHEMBL4100674 cxcr2_human Human Yes 9.0 IC50 = 1 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
414 4 3 5 3.2 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)[C@]2(C)CCOC2)c1O
CHEMBL3818323 cxcr2_human Human No 9.0 IC50 = 1 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
411 3 3 3 4.7 O=C(Nc1ccc(Cl)c(C(=O)N2CCCC2)c1O)Nc1cccc(F)c1Cl
CHEMBL3819382 cxcr2_human Human No 9.0 IC50 = 1 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
490 5 3 5 3.8 CCN1CCN(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c2O)CC1
CHEMBL446458 cxcr2_human Human Yes 9.0 IC50 = 1 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
384 6 3 7 2.7 C[C@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2[nH]c(=O)sc12
CHEMBL256668 cxcr2_human Human No 9.0 IC50 = 1 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
379 6 3 7 2.1 C[C@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2[nH]c(=O)cnc12
CHEMBL403225 cxcr2_human Human Yes 9.0 IC50 = 1 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
400 6 3 7 3.3 C[C@H](CO)Nc1nc(SCc2cccc(Cl)c2F)nc2[nH]c(=O)sc12
CHEMBL446458 cxcr2_human Human Yes 9.0 IC50 = 1 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
384 6 3 7 2.7 C[C@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2[nH]c(=O)sc12
CHEMBL4062546 cxcr2_human Human No 8.9 IC50 = 1.3 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
414 4 3 5 3.2 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2(C)CCOC2)c1O
CHEMBL4076478 cxcr2_human Human No 8.9 IC50 = 1.3 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
442 5 3 5 3.9 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)(C)[C@@H]2CCOC2)c1O
CHEMBL4079718 cxcr2_human Human No 8.9 IC50 = 1.3 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
446 5 3 5 3.6 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2(CF)CCOCC2)c1O
CHEMBL4084077 cxcr2_human Human No 8.9 IC50 = 1.3 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
402 6 3 5 3.1 COCC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)N[C@@H]2CCC=C2C)c1O
CHEMBL3818179 cxcr2_human Human No 8.9 IC50 = 1.3 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
477 4 3 5 4.5 CN1CC[C@H](S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(Cl)c3Cl)c2O)C1
CHEMBL3818331 cxcr2_human Human No 8.9 IC50 = 1.3 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
489 5 3 5 4.7 CCN1CCC(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c2O)CC1
CHEMBL246108 cxcr2_human Human Yes 8.9 IC50 = 1.3 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells by SPA
425 8 3 7 3.7 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(C(C)C)co1
CHEMBL4081963 cxcr2_human Human No 8.8 IC50 = 1.6 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
414 4 3 5 3.2 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2CCCOC2)c1O
CHEMBL4084135 cxcr2_human Human No 8.8 IC50 = 1.6 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
442 5 3 5 3.9 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)(C)[C@H]2CCOC2)c1O
CHEMBL4098536 cxcr2_human Human No 8.8 IC50 = 1.6 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
390 4 3 4 3.8 CC1=C(F)CCC1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)C)c1O
CHEMBL3819521 cxcr2_human Human No 8.8 IC50 = 1.6 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
491 4 3 5 4.9 CN1CCC(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(Cl)c3Cl)c2O)CC1
CHEMBL3819603 cxcr2_human Human No 8.8 IC50 = 1.6 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
504 5 3 5 4.2 CC(C)N1CCN(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c2O)CC1
CHEMBL4060060 cxcr2_human Human No 8.7 IC50 = 2.0 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
428 4 3 5 3.6 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2(C)CCCOC2)c1O
CHEMBL4072010 cxcr2_human Human No 8.7 IC50 = 2.0 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
437 6 3 5 3.2 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(F)(F)CN(C)C)c1O
CHEMBL3819070 cxcr2_human Human No 8.7 IC50 = 2.0 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
515 4 3 5 5.1 CN1CCC2(CC1)CC(S(=O)(=O)c1c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c1O)C2
CHEMBL3818269 cxcr2_human Human No 8.7 IC50 = 2.0 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
477 4 4 5 4.5 O=C(Nc1ccc(Cl)c(S(=O)(=O)C2CCNCC2)c1O)Nc1cccc(Cl)c1Cl
CHEMBL3819070 cxcr2_human Human No 8.7 IC50 = 2.0 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
515 4 3 5 5.1 CN1CCC2(CC1)CC(S(=O)(=O)c1c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c1O)C2
CHEMBL3819292 cxcr2_human Human Yes 8.7 IC50 = 2.0 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
409 3 4 4 3.6 NS(=O)(=O)c1c(Cl)ccc(NC(=O)Nc2cccc(Cl)c2Cl)c1O
CHEMBL3310786 cxcr2_human Human No 8.0 IC50 = 10 nM Funct
Antagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assayAntagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assay
363 5 2 6 2.8 N#Cc1c(O)nc(SCc2cccc(F)c2F)nc1[C@H]1C[C@@H]1C(=O)O
CHEMBL4064349 cxcr2_human Human No 8.0 IC50 = 10 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
376 4 3 4 3.4 CC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)NC2CCC=C2F)c1O
CHEMBL4068799 cxcr2_human Human No 8.0 IC50 = 10 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
406 4 3 4 4.0 CC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)NC2CCCC=C2Cl)c1O
CHEMBL4071768 cxcr2_human Human No 8.0 IC50 = 10 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
374 4 3 4 3.5 CC1CCCC1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)C)c1O
CHEMBL4090813 cxcr2_human Human No 8.0 IC50 = 10 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
372 4 3 4 3.5 CC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)NC2C=CCCC2)c1O
CHEMBL4093313 cxcr2_human Human No 8.0 IC50 = 10 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
360 4 3 4 3.3 CC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)NC2CCCC2)c1O
CHEMBL3817901 cxcr2_human Human No 8.0 IC50 = 10 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
420 4 3 4 4.7 CC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)Nc2cccc(F)c2Cl)c1O
CHEMBL3817880 cxcr2_human Human No 8.0 IC50 = 10 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
507 4 3 5 4.8 C[C@H]1CN(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(Cl)c3Cl)c2O)C[C@@H](C)O1
CHEMBL216981 cxcr2_human Human Yes 8.0 IC50 = 10 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
397 7 3 7 2.9 CC[C@H](c1ccc(o1)C)NC1=C(C(=O)C1=O)Nc1cccc(c1O)C(=O)N(C)C
CHEMBL4742368 cxcr2_human Human No 8.0 IC50 = 10 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
413 4 3 6 3.1 CC(C)S(=O)(=O)c1c(Cl)ccc(NC2=NC(=O)[C@@H](C3CCCCC3)N2)c1O
CHEMBL184185 cxcr2_human Human No 8.0 IC50 = 10 nM Bind
Concentration required to inhibit [125I]IL-8 binding towards C-X-C chemokine receptor type 2 of human expressed in CHO cellsConcentration required to inhibit [125I]IL-8 binding towards C-X-C chemokine receptor type 2 of human expressed in CHO cells
383 3 4 3 3.6 NC(=O)c1c(Cl)ccc(NC(=O)Nc2ccccc2Br)c1O
CHEMBL38182 cxcr2_human Human Yes 8.0 IC50 = 10 nM Bind
Displacement of [125I]IL-8 from CHO cell membranes expressing human CX3C chemokine receptor 2Displacement of [125I]IL-8 from CHO cell membranes expressing human CX3C chemokine receptor 2
356 2 3 4 3.2 N#Cc1ccc(NC(=O)Nc2ccccc2Br)c2nn[nH]c12
CHEMBL3403840 cxcr2_human Human No 8.0 IC50 = 10 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
422 8 3 7 2.8 C[C@H](CO)Nc1cc(NS(=O)(=O)C(F)(F)F)nc(SCc2ccccc2)n1
CHEMBL213130 cxcr2_human Human No 8.0 IC50 = 10 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells
357 3 3 6 1.8 CN(C)C(=O)c1cccc(/N=c2\c(O)c(O)\c2=N/C2CCCCC2)c1O
CHEMBL375175 cxcr2_human Human No 8.0 IC50 = 10 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells
317 3 3 6 0.9 CC(C)/N=c1\c(O)c(O)\c1=N/c1cccc(C(=O)N(C)C)c1O
CHEMBL1196279 cxcr2_human Human No 8.0 IC50 = 10 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
568 6 3 8 3.2 CN1CCCN(S(=O)(=O)c2c(Cl)ccc(Nc3c(Nc4ccccc4Br)c(=O)c3=O)c2O)CC1
CHEMBL556367 cxcr2_human Human No 8.0 IC50 = 10 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
568 6 3 8 3.2 CN1CCCN(S(=O)(=O)c2c(Cl)ccc(Nc3c(Nc4ccccc4Br)c(=O)c3=O)c2O)CC1
CHEMBL252697 cxcr2_human Human No 8.0 IC50 = 10.9 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
384 7 3 8 2.0 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cocn1
CHEMBL3355242 cxcr2_human Human No 7.0 IC50 = 100 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
453 5 3 6 3.9 CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nc(=O)cc(C(C)(C)C(F)(F)F)[nH]2)c1O
CHEMBL571141 cxcr2_human Human No 7.0 IC50 = 100 nM Funct
Antagonist activity at CXCR2 expressed in CHO cells assessed as inhibition of IL-8-induced chemotaxisAntagonist activity at CXCR2 expressed in CHO cells assessed as inhibition of IL-8-induced chemotaxis
424 8 3 8 2.3 CCN(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(OC)cc1
CHEMBL4076428 cxcr2_human Human No 7.0 IC50 = 100 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
453 5 3 5 3.7 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)[C@H]2C[C@H](N3CCCC3)C2)c1O
CHEMBL4079102 cxcr2_human Human No 7.0 IC50 = 100 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
404 5 3 4 3.8 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)(C)CF)c1O
CHEMBL4087900 cxcr2_human Human No 7.0 IC50 = 100 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
452 4 3 5 3.7 O=C(Nc1ccc(Cl)c(S(=O)(=O)C2(F)CCOCC2)c1O)N[C@H]1CCC=C1Cl
CHEMBL3818827 cxcr2_human Human No 7.0 IC50 = 100 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
489 4 3 5 4.7 CN1CCC[C@H](S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c2O)CC1
CHEMBL191413 cxcr2_human Human Yes 7.0 IC50 = 100 nM Bind
Binding affinity to CXCR2Binding affinity to CXCR2
283 5 1 3 2.1 CC(Cc1ccc(cc1)[C@H](C(=O)NS(=O)(=O)C)C)C
CHEMBL233262 cxcr2_human Human No 7.0 IC50 = 100 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
351 6 3 9 2.7 CC(C)(CO)Nc1nc(SCc2ccco2)nc2nc(N)sc12
CHEMBL395340 cxcr2_human Human No 7.0 IC50 = 100 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
439 9 3 8 4.7 CC[C@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2nc(NC(C)C)sc12
CHEMBL430381 cxcr2_human Human No 7.0 IC50 = 100 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
439 9 4 9 3.0 OCC(CO)Nc1nc(SCc2cccc(F)c2F)nc2nc(NC3CC3)sc12
CHEMBL3701187 cxcr2_human Human No 7.0 IC50 = 100 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
565 8 3 10 3.8 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N4CCC[C@@H]4C(=O)OC(C)(C)C)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL3701190 cxcr2_human Human No 7.0 IC50 = 100 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
438 8 3 8 3.7 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)C(C)C)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL4066904 cxcr2_human Human No 6.0 IC50 = 1000 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
445 5 3 5 4.0 CC1=CCC[C@H]1NC(=O)Nc1ccc(C#N)c(S(=O)(=O)C(C)(C)CC(F)(F)F)c1O
CHEMBL3819542 cxcr2_human Human No 6.0 IC50 = 1000 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
492 4 3 5 3.9 CN1CCN(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(Cl)c3Cl)c2O)CC1
CHEMBL3654434 cxcr2_human Human No 6.0 IC50 = 1000 nM Funct
Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.
397 8 2 4 3.6 CC(C)(NC(=O)c1ccc2c(c1OCCOc1ccccc1)CCCC2)C(=O)O
CHEMBL210448 cxcr2_human Human No 6.0 IC50 = 1000 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells
324 3 4 6 1.8 O=C(O)c1cccc(/N=c2\c(O)c(O)\c2=N/c2ccccc2)c1O
CHEMBL233264 cxcr2_human Human No 6.0 IC50 = 1000 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
382 6 3 10 2.9 Cc1nc(CSc2nc(NC(C)(C)CO)c3sc(N)nc3n2)cs1
CHEMBL60066 cxcr2_human Human No 6.0 IC50 = 1000 nM Bind
Evaluated using an SPA assay with recombinant human [125I]IL-8 and membranes prepared from Sf9 cells expressing human CXCR2Evaluated using an SPA assay with recombinant human [125I]IL-8 and membranes prepared from Sf9 cells expressing human CXCR2
266 2 1 2 2.4 O=C(Nc1ccc(F)cc1)c1ccc(Cl)[n+]([O-])c1
CHEMBL84755 cxcr2_human Human No 6.0 IC50 = 1000 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
301 3 1 4 3.9 Sc1nc(-c2cccc(Cl)c2)nn1Cc1ccccc1
CHEMBL3310793 cxcr2_human Human No 5.0 IC50 = 10000 nM Funct
Antagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assayAntagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assay
319 4 1 5 3.5 N#Cc1c(O)nc(CSc2cccc(F)c2F)nc1C1CC1
CHEMBL3818458 cxcr2_human Human No 5.0 IC50 = 10000 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
478 4 4 5 3.6 O=C(Nc1ccc(Cl)c(S(=O)(=O)N2CCNCC2)c1O)Nc1cccc(Cl)c1Cl
CHEMBL201672 cxcr2_human Human No 5.0 IC50 = 10000 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPADisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPA
255 5 1 6 3.1 CCCCCSc1nc(O)c2scnc2n1
CHEMBL201799 cxcr2_human Human No 5.0 IC50 = 10000 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPADisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPA
270 5 2 7 2.7 CCCCCSc1nc(O)c2sc(N)nc2n1
CHEMBL201800 cxcr2_human Human No 5.0 IC50 = 10000 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPADisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPA
289 3 2 7 2.5 Nc1nc2nc(SCc3ccccc3)nc(N)c2s1
CHEMBL195433 cxcr2_human Human Yes 5.0 IC50 = 10000 nM Bind
Inhibition of C-X-C chemokine receptor type 2Inhibition of C-X-C chemokine receptor type 2
486 7 2 5 5.4 CC(=O)c1sc(NC(=O)N[C@@H]2CCCC[C@H]2CN2CCC[C@@H](Cc3ccc(F)cc3)C2)nc1C
CHEMBL363840 cxcr2_human Human No 5.0 IC50 = 10000 nM Bind
Inhibition of C-X-C chemokine receptor type 2Inhibition of C-X-C chemokine receptor type 2
505 7 2 6 4.7 Cn1nnnc1-c1cccc(NC(=O)N[C@@H]2CCCC[C@H]2CN2CCC[C@@H](Cc3ccc(F)cc3)C2)c1
CHEMBL84752 cxcr2_human Human No 5.0 IC50 = 10000 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
365 4 1 5 4.6 COc1ccc(Cn2nc(-c3ccc(Cl)cc3Cl)nc2S)cc1
CHEMBL3658347 cxcr2_human Human No 5.0 IC50 = 10230 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
387 5 2 6 2.5 O=C(Nc1ccc(F)cn1)c1ccc(S(=O)(=O)Cc2ccccc2O)nc1
CHEMBL1437942 cxcr2_human Human No 5.0 IC50 = 10300 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
271 3 1 5 3.0 Cc1cc2nc(CSc3ccccc3)cc(O)n2n1
CHEMBL3704566 cxcr2_human Human No 6.0 IC50 = 1035 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
399 7 3 9 2.2 COc1ccc(Nc2c(NC(c3ccc(C)o3)C3(C)COC3)c(=O)c2=O)c(O)n1
CHEMBL3342318 cxcr2_human Human No 7.0 IC50 = 105 nM Funct
Antagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assay
380 6 4 6 2.0 O=C(Nc1ccc(O)cc1)c1ccc(SCc2ccccc2B(O)O)nc1
CHEMBL3342318 cxcr2_human Human No 7.0 IC50 = 105 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
380 6 4 6 2.0 O=C(Nc1ccc(O)cc1)c1ccc(SCc2ccccc2B(O)O)nc1
CHEMBL3104898 cxcr2_human Human No 5.0 IC50 = 10500 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
319 5 1 5 2.3 COc1cc(CCc2cccc(F)c2F)nc2cc(CO)nn12
CHEMBL3906175 cxcr2_human Human No 7.0 IC50 = 106 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
555 9 2 9 4.3 CCOC(=O)[C@@H]1CCCN1C(=O)c1cccc(Nc2c(NC(c3ccc(C)o3)C3CCCS3)c(=O)c2=O)c1F
CHEMBL3701184 cxcr2_human Human No 7.0 IC50 = 106 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
453 8 3 8 2.9 CCC1(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)c2ccc(C)o2)COC1
CHEMBL3704561 cxcr2_human Human No 7.0 IC50 = 106 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
441 7 3 8 2.7 CN(C)C(=O)c1cccc(Nc2c(NC(c3cccs3)C3(C)COC3)c(=O)c2=O)c1O
CHEMBL3654442 cxcr2_human Human No 6.0 IC50 = 1060 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
480 7 1 6 5.6 CC(=O)Oc1ccc(OC(F)(F)F)cc1CSc1ccc(C(=O)Nc2ccc(F)cc2)cn1
CHEMBL4800160 cxcr2_human Human No 5.0 IC50 = 10600 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
486 4 2 5 6.9 CC1CCCc2sc(NC(=S)Nc3ccc(OC(F)(F)F)cc3)c(C(=O)OC(C)(C)C)c21
CHEMBL3701186 cxcr2_human Human No 6.0 IC50 = 1088 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
481 7 4 9 2.0 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N4CC[C@H](O)C4)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL3976863 cxcr2_human Human No 7.0 IC50 = 109 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
569 9 2 9 4.7 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N4CCC[C@H]4C(=O)OC(C)C)c3F)c(=O)c2=O)C2CCCS2)o1
CHEMBL24912 cxcr2_human Human Yes 5.0 IC50 = 10900 nM Bind
Inhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 2 expressed in CHO Cells using [125I]IL-8 radioligandInhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 2 expressed in CHO Cells using [125I]IL-8 radioligand
273 3 3 4 2.9 O=C(Nc1ccccc1)Nc1cc([N+](=O)[O-])ccc1O
CHEMBL39740 cxcr2_human Human Yes 7.0 IC50 = 110 nM Bind
Compound binding was evaluated using an SPA assay with recombinant human [125I]IL-8 and membranes prepared from Sf9 cells expressing human C-X-C chemokine receptor type 2Compound binding was evaluated using an SPA assay with recombinant human [125I]IL-8 and membranes prepared from Sf9 cells expressing human C-X-C chemokine receptor type 2
504 10 1 6 7.9 CCN(CC)CCCCNc1nc2cc(Cl)c(Cl)cc2nc1-c1ccc(-c2cccs2)s1
CHEMBL39740 cxcr2_human Human Yes 7.0 IC50 = 110 nM Bind
Displacement of [125I]IL-8 from CHO cell membranes expressing human CX3C chemokine receptor 2Displacement of [125I]IL-8 from CHO cell membranes expressing human CX3C chemokine receptor 2
504 10 1 6 7.9 CCN(CC)CCCCNc1nc2cc(Cl)c(Cl)cc2nc1-c1ccc(-c2cccs2)s1
CHEMBL4776480 cxcr2_human Human No 6.0 IC50 = 1100 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
408 3 2 5 4.7 CC(C)(C)OC(=O)c1c(NC(=S)Nc2ccc(F)cc2)sc2c1CCOC2
CHEMBL3609005 cxcr2_human Human No 6.0 IC50 = 1100 nM Funct
Antagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysisAntagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysis
379 6 3 5 1.8 CN(Cc1ccc(B(O)O)cc1)c1ccc(C(=O)Nc2ccc(F)cc2)cn1
CHEMBL231924 cxcr2_human Human No 6.0 IC50 = 1100 nM Funct
Antagonist activity at CXCR2 receptor expressed in CHOK1 cells assessed as human IL8-induced calcium mobilization by FLIPRAntagonist activity at CXCR2 receptor expressed in CHOK1 cells assessed as human IL8-induced calcium mobilization by FLIPR
368 2 3 7 2.5 O=[N+]([O-])c1cc(O)c2c(c1)S(=O)(=O)N=C(Nc1ccccc1Cl)N2
CHEMBL3104899 cxcr2_human Human No 6.0 IC50 = 1100 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
305 4 2 5 2.0 OCc1cc2nc(CCc3cccc(F)c3F)cc(O)n2n1
CHEMBL258038 cxcr2_human Human No 6.0 IC50 = 1100 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
456 10 3 4 3.9 CCCCNS(=O)(=O)NC(=O)CCCc1c(-c2ccc(F)cc2)[nH]c2ccc(C#N)cc12
CHEMBL403497 cxcr2_human Human No 6.0 IC50 = 1100 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
456 9 2 4 3.9 CCN(CC)S(=O)(=O)NC(=O)CCCc1c(-c2ccc(F)cc2)[nH]c2ccc(C#N)cc12
CHEMBL3104904 cxcr2_human Human No 5.0 IC50 = 11000 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
431 6 1 8 4.8 Oc1cc(CSc2nc(-c3ccccc3)cs2)nc2nc(Cc3ccccc3)nn12
CHEMBL3104906 cxcr2_human Human No 5.0 IC50 = 11000 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
408 7 1 8 3.7 COc1ccc(SCc2cc(O)n3nc(Cc4ccccc4)nc3n2)c(OC)c1
CHEMBL3915853 cxcr2_human Human No 7.0 IC50 = 111 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the beta -arrestin recruitment after receptor activation type.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 beta -arrestin line results in the recruitment of beta -arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation.>>J. Immunol. 170: 2904-2911).In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with beta -arrestin 2, a beta -arrestin 2 recruitment test for CXCR2 or CXCR1 based on beta -galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the beta -arrestin recruitment after receptor activation type.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 beta -arrestin line results in the recruitment of beta -arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation.>>J. Immunol. 170: 2904-2911).In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with beta -arrestin 2, a beta -arrestin 2 recruitment test for CXCR2 or CXCR1 based on beta -galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
469 7 3 8 3.6 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2CCSCC2)o1
CHEMBL218334 cxcr2_human Human No 7.0 IC50 = 112 nM Bind
Displacement of [125I]IL8 from CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR2 expressed in CHO cells
435 5 3 5 3.8 CC(C)c1ccccc1N/C(=N\C#N)Nc1ccc(Cl)c(S(=O)(=O)N(C)C)c1O
CHEMBL3658241 cxcr2_human Human No 7.0 IC50 = 112 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
464 6 1 5 5.1 CC1(C)OB(c2ccc(CSc3ccc(C(=O)Nc4ccc(F)cc4)cn3)cc2)OC1(C)C
CHEMBL1188250 cxcr2_human Human No 6.9 IC50 = 114 nM Bind
Concentration required to inhibit [125I]IL-8 binding towards C-X-C chemokine receptor type 2 of human expressed in CHO cellsConcentration required to inhibit [125I]IL-8 binding towards C-X-C chemokine receptor type 2 of human expressed in CHO cells
369 3 4 3 3.9 NCc1c(Cl)ccc(NC(=O)Nc2ccccc2Br)c1O
CHEMBL535818 cxcr2_human Human No 6.9 IC50 = 114 nM Bind
Concentration required to inhibit [125I]IL-8 binding towards C-X-C chemokine receptor type 2 of human expressed in CHO cellsConcentration required to inhibit [125I]IL-8 binding towards C-X-C chemokine receptor type 2 of human expressed in CHO cells
369 3 4 3 3.9 NCc1c(Cl)ccc(NC(=O)Nc2ccccc2Br)c1O
CHEMBL3902863 cxcr2_human Human No 6.9 IC50 = 115 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
523 8 3 8 4.3 Cc1ccc([C@@H](Nc2c(Nc3cccc(C(=O)N(C)CC(F)(F)F)c3O)c(=O)c2=O)C2CCCS2)o1
CHEMBL3658288 cxcr2_human Human No 5.9 IC50 = 1150 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
434 7 2 7 3.6 O=C(CSc1ccc(C(=O)Nc2ccc(F)cc2)cn1)c1ccc(-c2nn[nH]n2)cc1
CHEMBL3658340 cxcr2_human Human No 6.9 IC50 = 116 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
384 6 3 7 1.2 O=C(Nc1ccc(F)cn1)c1cnc(SCc2ccccc2B(O)O)nc1
CHEMBL3658349 cxcr2_human Human No 5.9 IC50 = 1190 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
471 6 2 7 3.4 O=C(Nc1ccc(F)cn1)c1ccc(S(=O)(=O)Cc2cc(OC(F)(F)F)ccc2O)nc1
CHEMBL183222 cxcr2_human Human No 7.9 IC50 = 12 nM Bind
Concentration required to inhibit [125I]IL-8 binding towards C-X-C chemokine receptor type 2 of human expressed in CHO cellsConcentration required to inhibit [125I]IL-8 binding towards C-X-C chemokine receptor type 2 of human expressed in CHO cells
447 4 3 4 3.7 CN(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)Nc2ccccc2Br)c1O
CHEMBL218744 cxcr2_human Human No 7.9 IC50 = 12 nM Bind
Displacement of [125I]IL8 from CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR2 expressed in CHO cells
564 8 4 7 3.6 CCC(CC)(NS(=O)(=O)c1cccc(N/C(=N/C#N)Nc2ccccc2Br)c1O)N1CCOCC1
CHEMBL222075 cxcr2_human Human No 7.9 IC50 = 12 nM Bind
Displacement of [125I]IL8 from CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR2 expressed in CHO cells
461 4 3 5 3.7 CN(C)S(=O)(=O)c1c(Cl)ccc(N/C(=N/C#N)Nc2ccccc2C(F)(F)F)c1O
CHEMBL253927 cxcr2_human Human No 7.9 IC50 = 12.2 nM Bind
Inhibition of CXCR2-mediated chemotaxis in Ba/F3 cells expressing human CXCR2Inhibition of CXCR2-mediated chemotaxis in Ba/F3 cells expressing human CXCR2
398 7 3 8 2.3 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(C)on1
CHEMBL4062881 cxcr2_human Human No 7.9 IC50 = 12.6 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
386 4 3 4 3.8 CC1=CCCCC1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)C)c1O
CHEMBL3818984 cxcr2_human Human No 7.9 IC50 = 12.6 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
432 4 3 4 4.8 O=C(Nc1ccc(Cl)c(S(=O)(=O)C2CCC2)c1O)Nc1cccc(F)c1Cl
CHEMBL3403835 cxcr2_human Human No 7.9 IC50 = 12.6 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
420 8 3 7 2.7 C[C@H](CO)Nc1cc(NS(C)(=O)=O)nc(SCc2cccc(Cl)c2F)n1
CHEMBL3403847 cxcr2_human Human No 7.9 IC50 = 12.6 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
486 9 3 9 2.9 C[C@H](CO)Nc1cc(NS(=O)(=O)c2cn(C)cn2)nc(SCc2cccc(Cl)c2F)n1
CHEMBL232846 cxcr2_human Human No 7.9 IC50 = 12.6 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
365 6 3 8 2.9 C[C@H](CO)Nc1nc(SCc2ccccc2F)nc2nc(N)sc12
CHEMBL394799 cxcr2_human Human No 7.9 IC50 = 12.6 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
381 6 3 8 3.4 C[C@H](CO)Nc1nc(SCc2cccc(Cl)c2)nc2nc(N)sc12
CHEMBL390191 cxcr2_human Human No 6.9 IC50 = 120 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
368 6 3 10 2.5 Cc1nc(CSc2nc(N[C@H](C)CO)c3sc(N)nc3n2)cs1
CHEMBL274737 cxcr2_human Human No 6.9 IC50 = 120 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPADisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPA
361 7 3 8 3.1 CC[C@H](CO)Nc1nc(SCc2ccccc2)nc2nc(N)sc12
CHEMBL254773 cxcr2_human Human No 6.9 IC50 = 120 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
515 6 3 3 5.0 O=C(NCCc1c(-c2ccc(F)cc2)[nH]c2ccc(Br)cc12)NS(=O)(=O)c1ccccc1
CHEMBL257829 cxcr2_human Human No 6.9 IC50 = 120 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
414 7 3 4 2.7 CNS(=O)(=O)NC(=O)CCCc1c(-c2ccc(F)cc2)[nH]c2ccc(C#N)cc12
CHEMBL234396 cxcr2_human Human No 6.9 IC50 = 120 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cells
419 1 3 5 3.5 O=S1(=O)N=C(Nc2ccc(F)cc2Br)Nc2c(O)cc(Cl)cc21
CHEMBL39835 cxcr2_human Human No 5.9 IC50 = 1200 nM Bind
Displacement of [125I]IL-8 from CHO cell membranes expressing human CX3C chemokine receptor 2 (CXCR2 filter mat binding assay)Displacement of [125I]IL-8 from CHO cell membranes expressing human CX3C chemokine receptor 2 (CXCR2 filter mat binding assay)
306 5 2 4 2.7 O=C(O)CSc1ccc(C(=O)Nc2ccc(F)cc2)cn1
CHEMBL3609011 cxcr2_human Human No 6.9 IC50 = 121 nM Funct
Antagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysisAntagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysis
380 6 3 6 1.2 CN(Cc1ccc(B(O)O)cc1)c1ncc(C(=O)Nc2ccc(F)cc2)cn1
CHEMBL3342290 cxcr2_human Human No 5.9 IC50 = 1210 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
435 6 1 5 6.2 Cc1nc(-c2ccccc2)sc1CSc1ccc(C(=O)Nc2ccc(F)cc2)cn1
CHEMBL3654445 cxcr2_human Human No 5.9 IC50 = 1230 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
482 6 1 5 5.2 CC1(C)OB(c2ccc(F)cc2CSc2ccc(C(=O)Nc3ccc(F)cc3)cn2)OC1(C)C
CHEMBL3658336 cxcr2_human Human No 5.9 IC50 = 1230 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
456 8 1 4 6.0 O=C(Nc1ccc(F)cc1)c1ccc(SCC(=O)C(c2ccccc2)c2ccccc2)nc1
CHEMBL3658348 cxcr2_human Human No 5.9 IC50 = 1230 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
455 6 2 6 3.8 O=C(Nc1ccc(F)cn1)c1ccc([S+]([O-])Cc2cc(OC(F)(F)F)ccc2O)nc1
CHEMBL3355234 cxcr2_human Human No 6.9 IC50 = 125.9 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
399 6 3 6 3.3 CC(C)Cc1cc(=O)nc(Nc2ccc(Cl)c(S(=O)(=O)C(C)C)c2O)[nH]1
CHEMBL3355241 cxcr2_human Human No 6.9 IC50 = 125.9 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
417 6 3 6 3.3 CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nc(=O)cc(C(C)(C)CF)[nH]2)c1O
CHEMBL3355243 cxcr2_human Human No 6.9 IC50 = 125.9 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
403 5 3 6 3.3 CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nc(=O)cc(C(C)(C)F)[nH]2)c1O
CHEMBL4062546 cxcr2_human Human No 6.9 IC50 = 125.9 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
414 4 3 5 3.2 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2(C)CCOC2)c1O
CHEMBL4097602 cxcr2_human Human No 6.9 IC50 = 125.9 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
427 5 3 5 3.1 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)[C@H]2C[C@H](N(C)C)C2)c1O
CHEMBL4065522 cxcr2_human Human No 6.9 IC50 = 125.9 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
429 6 3 5 3.4 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)(C)CN(C)C)c1O
CHEMBL390191 cxcr2_human Human No 6.9 IC50 = 125.9 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
368 6 3 10 2.5 Cc1nc(CSc2nc(N[C@H](C)CO)c3sc(N)nc3n2)cs1
CHEMBL576886 cxcr2_human Human No 5.9 IC50 = 1250 nM Funct
Antagonist activity at CXCR2 expressed in CHO cells assessed as inhibition of IL-8-induced chemotaxisAntagonist activity at CXCR2 expressed in CHO cells assessed as inhibition of IL-8-induced chemotaxis
360 6 3 7 0.6 CCN(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)C(C)=O
CHEMBL3645133 cxcr2_human Human No 5.9 IC50 = 1250 nM Funct
Calcium Fluorescence Assay (FLIPR) : CXCR2 inhibition using calcium fluorescence assay (FLIPR).Calcium Fluorescence Assay (FLIPR) : CXCR2 inhibition using calcium fluorescence assay (FLIPR).
445 8 2 4 4.7 CC(C)(NC(=O)c1ccc2ccccc2c1OCCOc1ccc(F)c(Cl)c1)C(=O)O
CHEMBL3658311 cxcr2_human Human No 5.9 IC50 = 1250 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
500 6 1 5 6.4 O=C(Nc1ccc(F)cc1)c1ccc(SCC(=O)c2csc3ccc(Br)cc23)nc1
CHEMBL3956663 cxcr2_human Human No 5.9 IC50 = 1253 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
469 7 3 9 2.6 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)[C@@H]2COC(C)(C)O2)o1
CHEMBL4088965 cxcr2_human Human No 5.9 IC50 = 1258.9 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
376 4 3 5 2.5 CC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)NC2CCOCC2)c1O
CHEMBL271013 cxcr2_human Human No 7.9 IC50 = 13 nM Bind
Displacement of [125I]-IL8 from human CXCR2 transfected in HEK293 cells after 4 hrs by microbeta counting analysisDisplacement of [125I]-IL8 from human CXCR2 transfected in HEK293 cells after 4 hrs by microbeta counting analysis
347 6 3 8 2.8 C[C@H](CO)Nc1nc(SCc2ccccc2)nc2nc(N)sc12
CHEMBL425985 cxcr2_human Human No 7.9 IC50 = 13 nM Bind
Displacement of [125I]IL8 from CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR2 expressed in CHO cells
469 5 3 5 4.3 CN(C)S(=O)(=O)c1c(Cl)ccc(N/C(=N/C#N)Nc2ccccc2-c2ccccc2)c1O
CHEMBL1182475 cxcr2_human Human No 7.9 IC50 = 13 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
538 6 3 8 2.3 CN1CCN(S(=O)(=O)c2c(F)ccc(Nc3c(Nc4ccccc4Br)c(=O)c3=O)c2O)CC1
CHEMBL239982 cxcr2_human Human No 7.9 IC50 = 13 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
538 6 3 8 2.3 CN1CCN(S(=O)(=O)c2c(F)ccc(Nc3c(Nc4ccccc4Br)c(=O)c3=O)c2O)CC1
CHEMBL232846 cxcr2_human Human No 7.9 IC50 = 13 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
365 6 3 8 2.9 C[C@H](CO)Nc1nc(SCc2ccccc2F)nc2nc(N)sc12
CHEMBL257006 cxcr2_human Human No 7.9 IC50 = 13 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
366 6 4 7 2.3 C[C@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2[nH]c(N)nc12
CHEMBL271013 cxcr2_human Human No 7.9 IC50 = 13 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
347 6 3 8 2.8 C[C@H](CO)Nc1nc(SCc2ccccc2)nc2nc(N)sc12
CHEMBL294095 cxcr2_human Human No 6.9 IC50 = 130 nM Bind
Evaluated using an SPA assay with recombinant human [125I]IL-8 and membranes prepared from Sf9 cells expressing human CXCR2Evaluated using an SPA assay with recombinant human [125I]IL-8 and membranes prepared from Sf9 cells expressing human CXCR2
324 4 1 4 1.5 CCS(=O)(=O)c1ccc(C(=O)Nc2ccc(F)cc2)c[n+]1[O-]
CHEMBL61835 cxcr2_human Human No 6.9 IC50 = 130 nM Bind
Evaluated using an SPA assay with recombinant human [125I]IL-8 and membranes prepared from Sf9 cells expressing human CXCR2Evaluated using an SPA assay with recombinant human [125I]IL-8 and membranes prepared from Sf9 cells expressing human CXCR2
310 3 1 4 1.1 CS(=O)(=O)c1ccc(C(=O)Nc2ccc(F)cc2)c[n+]1[O-]
CHEMBL3426944 cxcr2_human Human Yes 6.9 IC50 = 130 nM Bind
Inhibition of CXCR2 (unknown origin) expressed in PathHunter celline by beta-arrestin assayInhibition of CXCR2 (unknown origin) expressed in PathHunter celline by beta-arrestin assay
466 7 3 6 3.3 O=C(Nc1ccc(F)cc1)c1ccc(SCc2cc(OC(F)(F)F)ccc2B(O)O)nc1
CHEMBL3310785 cxcr2_human Human No 5.9 IC50 = 1300 nM Funct
Antagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assayAntagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assay
391 6 1 7 3.3 CCOC(=O)[C@H]1C[C@@H]1c1nc(SCc2cccc(F)c2F)nc(O)c1C#N
CHEMBL257829 cxcr2_rabit Rabbit No 5.9 IC50 = 1300 nM Funct
Antagonist activity at rabbit CXCR2 by neutrophil chemotaxis assayAntagonist activity at rabbit CXCR2 by neutrophil chemotaxis assay
414 7 3 4 2.7 CNS(=O)(=O)NC(=O)CCCc1c(-c2ccc(F)cc2)[nH]c2ccc(C#N)cc12
CHEMBL373067 cxcr2_human Human Yes 5.9 IC50 = 1300 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPADisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPA
290 3 2 7 2.7 Nc1nc2nc(SCc3ccccc3)nc(O)c2s1
CHEMBL258438 cxcr2_human Human No 5.9 IC50 = 1300 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
427 8 2 4 4.0 CCCS(=O)(=O)NC(=O)CCCc1c(-c2ccc(F)cc2)[nH]c2ccc(C#N)cc12
CHEMBL3104905 cxcr2_human Human No 4.9 IC50 = 13000 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
374 5 1 8 3.0 N#Cc1cccnc1SCc1cc(O)n2nc(Cc3ccccc3)nc2n1
CHEMBL3951994 cxcr2_human Human No 6.9 IC50 = 134 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
455 7 3 8 3.4 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2CCCS2)o1
CHEMBL3951994 cxcr2_human Human No 6.9 IC50 = 135 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
455 7 3 8 3.4 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2CCCS2)o1
CHEMBL11359 cxcr2_human Human No 4.9 IC50 = 13516 nM Bind
DRUGMATRIX: Chemokine CXCR2 (IL-8B) radioligand binding (ligand: [125I] IL-8)DRUGMATRIX: Chemokine CXCR2 (IL-8B) radioligand binding (ligand: [125I] IL-8)
None None None None
CHEMBL2068237 cxcr2_human Human No 4.9 IC50 = 13516 nM Bind
DRUGMATRIX: Chemokine CXCR2 (IL-8B) radioligand binding (ligand: [125I] IL-8)DRUGMATRIX: Chemokine CXCR2 (IL-8B) radioligand binding (ligand: [125I] IL-8)
None None None None
CHEMBL436940 cxcr2_human Human No 6.9 IC50 = 139 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells
413 6 4 6 3.2 O=C(NCc1ccccc1)c1cccc(Nc2c(O)c(=O)/c2=N\c2ccccc2)c1O
CHEMBL3104897 cxcr2_human Human No 4.9 IC50 = 13900 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
461 7 1 7 3.7 CS(=O)(=O)Nc1cc(CSc2cccc(F)c2F)nc2nc(Cc3ccccc3)nn12
CHEMBL257829 cxcr2_human Human No 7.9 IC50 = 14 nM Funct
Antagonist activity at human cloned CXCR2 by calcium flux FLIPR assayAntagonist activity at human cloned CXCR2 by calcium flux FLIPR assay
414 7 3 4 2.7 CNS(=O)(=O)NC(=O)CCCc1c(-c2ccc(F)cc2)[nH]c2ccc(C#N)cc12
CHEMBL211247 cxcr2_human Human No 7.9 IC50 = 14 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells
331 2 3 6 1.3 CN(C)C(=O)c1cccc(/N=c2\c(O)c(O)\c2=N/C(C)(C)C)c1O
CHEMBL238743 cxcr2_human Human No 7.9 IC50 = 14 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
357 5 4 6 2.2 NC(=O)c1c(Cl)ccc(Nc2c(Nc3ccccc3)c(=O)c2=O)c1O
CHEMBL380947 cxcr2_human Human No 7.9 IC50 = 14 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPADisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPA
397 6 3 8 3.4 CC(C)(CO)Nc1nc(SCc2cccc(F)c2F)nc2nc(N)sc12
CHEMBL3658321 cxcr2_human Human No 7.9 IC50 = 14 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
415 7 1 8 3.2 COC(=O)c1cc(C(=O)CSc2ccc(C(=O)Nc3ccc(F)cc3)cn2)on1
CHEMBL3310783 cxcr2_human Human Yes 6.9 IC50 = 140 nM Funct
Antagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assayAntagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assay
319 4 1 5 3.5 N#Cc1c(O)nc(SCc2cccc(F)c2F)nc1C1CC1
CHEMBL4750465 cxcr2_human Human No 6.9 IC50 = 140 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
359 4 3 6 1.9 CCC1NC(Nc2ccc(Cl)c(S(=O)(=O)C(C)C)c2O)=NC1=O
CHEMBL403702 cxcr2_human Human No 6.9 IC50 = 140 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
377 6 2 7 3.1 Cc1cnc2nc(SCc3cccc(F)c3F)nc(N[C@H](C)CO)c2n1
CHEMBL254978 cxcr2_human Human No 6.9 IC50 = 140 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
462 6 3 4 4.1 N#Cc1ccc2[nH]c(-c3ccc(F)cc3)c(CCNC(=O)NS(=O)(=O)c3ccccc3)c2c1
CHEMBL3310773 cxcr2_human Human No 5.9 IC50 = 1400 nM Funct
Antagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assayAntagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assay
369 4 1 5 4.6 Cc1ccc(-c2nc(SCc3cccc(F)c3F)nc(O)c2C#N)cc1
CHEMBL3311396 cxcr2_human Human No 5.9 IC50 = 1400 nM Funct
Antagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assayAntagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assay
372 4 1 4 4.4 Oc1nc(SCc2cccc(F)c2F)nc(C2CC2)c1Br
CHEMBL3654433 cxcr2_human Human No 5.9 IC50 = 1400 nM Funct
Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.
387 7 2 3 4.5 CC(C)(NC(=O)c1ccc2c(c1OCCC1CCCCC1)CCCC2)C(=O)O
CHEMBL201204 cxcr2_human Human No 5.9 IC50 = 1400 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPADisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPA
453 9 3 9 4.9 CC[C@@H](CO)Nc1nc(SCc2cccc(Oc3ccccc3)c2)nc2nc(N)sc12
CHEMBL404062 cxcr2_human Human No 5.9 IC50 = 1400 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
475 8 2 4 4.8 N#Cc1ccc2[nH]c(-c3ccc(F)cc3)c(CCCC(=O)NS(=O)(=O)Cc3ccccc3)c2c1
CHEMBL84957 cxcr2_human Human No 5.9 IC50 = 1400 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
297 4 1 5 3.3 COc1ccccc1-c1nc(S)n(Cc2ccccc2)n1
CHEMBL87282 cxcr2_human Human No 5.9 IC50 = 1400 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
281 3 1 4 3.6 Cc1ccccc1-c1nc(S)n(Cc2ccccc2)n1
CHEMBL214162 cxcr2_human Human No 6.8 IC50 = 144.8 nM Funct
Inhibition of chemotaxis of CHO cells expressing human CXCR2Inhibition of chemotaxis of CHO cells expressing human CXCR2
343 3 3 6 1.5 CN(C)C(=O)c1cccc(/N=c2\c(O)c(O)\c2=N/C2CCCC2)c1O
CHEMBL3704562 cxcr2_human Human No 6.8 IC50 = 146 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
455 7 3 8 3.0 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)COC2)s1
CHEMBL3342311 cxcr2_human Human No 5.8 IC50 = 1480 nM Funct
Antagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assay
382 6 2 4 4.5 O=C(Nc1ccc(F)cc1)c1ccc(SCc2ccccc2C(=O)O)nc1
CHEMBL3342311 cxcr2_human Human No 5.8 IC50 = 1480 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
382 6 2 4 4.5 O=C(Nc1ccc(F)cc1)c1ccc(SCc2ccccc2C(=O)O)nc1
CHEMBL4536494 cxcr2_human Human No 4.8 IC50 = 14800 nM Funct
Antagonist activity at CXCR2 (unknown origin) stably expressed in HEK293 cells co-expressing Galpha16 assessed as reduction in IL-8-induced intracellular calcium change incubated for 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity at CXCR2 (unknown origin) stably expressed in HEK293 cells co-expressing Galpha16 assessed as reduction in IL-8-induced intracellular calcium change incubated for 10 mins by Fluo-4AM dye based fluorescence assay
392 5 3 6 3.8 CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nnc(-c3ccccc3)[nH]2)c1O
CHEMBL4757674 cxcr2_human Human No 7.8 IC50 = 15 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
522 7 4 8 3.4 CC(C)(C)OC(=O)NCCCS(=O)(=O)c1c(Cl)ccc(NC2=NC(=O)C(c3ccccc3)N2)c1O
CHEMBL386505 cxcr2_human Human No 7.8 IC50 = 15 nM Bind
Displacement of [125I]IL8 from CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR2 expressed in CHO cells
421 5 3 5 3.2 CCc1ccccc1N/C(=N\C#N)Nc1ccc(Cl)c(S(=O)(=O)N(C)C)c1O
CHEMBL209859 cxcr2_human Human No 7.8 IC50 = 15 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
305 3 3 6 2.2 N#Cc1ccc(Nc2c(O)c(=O)/c2=N\c2ccccc2)c(O)c1
CHEMBL239136 cxcr2_human Human No 7.8 IC50 = 15 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
383 4 3 6 3.1 N#Cc1ccc(Nc2c(Nc3ccccc3Br)c(=O)c2=O)c(O)c1
CHEMBL239768 cxcr2_human Human No 7.8 IC50 = 15 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
415 6 3 7 2.3 Cc1ccccc1Nc1c(Nc2ccc(C)c(S(=O)(=O)N(C)C)c2O)c(=O)c1=O
CHEMBL218964 cxcr2_human Human No 7.8 IC50 = 15 nM Bind
Displacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cells
345 7 3 6 2.0 CCC(CC)Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O
CHEMBL3909470 cxcr2_human Human No 7.8 IC50 = 15 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
523 8 3 8 4.3 Cc1ccc([C@H](Nc2c(Nc3cccc(C(=O)N(C)CC(F)(F)F)c3O)c(=O)c2=O)C2CCCS2)o1
CHEMBL3951994 cxcr2_human Human No 7.8 IC50 = 15 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
455 7 3 8 3.4 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2CCCS2)o1
CHEMBL3355237 cxcr2_human Human No 7.8 IC50 = 15.9 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
397 5 3 6 3.3 CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nc(=O)cc(C3CCC3)[nH]2)c1O
CHEMBL3355240 cxcr2_human Human No 7.8 IC50 = 15.9 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
411 5 3 6 3.5 CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nc(=O)cc(C3(C)CCC3)[nH]2)c1O
CHEMBL380947 cxcr2_human Human No 7.8 IC50 = 15.9 nM Funct
Antagonistic activity against human CXCR2 in neutrophils assessed as blockade of GROalpha stimulated calcium mobilisation by FLIPRAntagonistic activity against human CXCR2 in neutrophils assessed as blockade of GROalpha stimulated calcium mobilisation by FLIPR
397 6 3 8 3.4 CC(C)(CO)Nc1nc(SCc2cccc(F)c2F)nc2nc(N)sc12
CHEMBL233059 cxcr2_human Human No 7.8 IC50 = 15.9 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
365 6 3 8 2.9 C[C@H](CO)Nc1nc(SCc2cccc(F)c2)nc2nc(N)sc12
CHEMBL233260 cxcr2_human Human No 7.8 IC50 = 15.9 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
415 6 3 8 4.1 C[C@H](CO)Nc1nc(SCc2cccc(Cl)c2Cl)nc2nc(N)sc12
CHEMBL389791 cxcr2_human Human No 7.8 IC50 = 15.9 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
413 7 4 9 2.4 C[C@@H](O)[C@@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2nc(N)sc12
CHEMBL38182 cxcr2_human Human Yes 6.8 IC50 = 150 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
356 2 3 4 3.2 N#Cc1ccc(NC(=O)Nc2ccccc2Br)c2nn[nH]c12
CHEMBL3105080 cxcr2_human Human No 6.8 IC50 = 150 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
359 4 1 6 4.3 Oc1cc(CSc2cccc(F)c2F)nc2cc(-c3ccco3)nn12
CHEMBL254366 cxcr2_human Human No 6.8 IC50 = 150 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
470 7 2 5 2.9 N#Cc1ccc2[nH]c(-c3ccc(F)cc3)c(CCCC(=O)NS(=O)(=O)N3CCOCC3)c2c1
CHEMBL254308 cxcr2_human Human No 6.8 IC50 = 150 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
527 8 3 7 5.3 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(-c2ccccc2C(F)(F)F)o1
CHEMBL3310785 cxcr2_human Human No 5.8 IC50 = 1500 nM Funct
Antagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assayAntagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assay
391 6 1 7 3.3 CCOC(=O)[C@H]1C[C@@H]1c1nc(SCc2cccc(F)c2F)nc(O)c1C#N
CHEMBL3102879 cxcr2_human Human No 5.8 IC50 = 1500 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
308 3 1 6 2.7 Cc1nc2nc(CSc3cccc(F)c3F)cc(O)n2n1
CHEMBL4536494 cxcr2_human Human No 4.8 IC50 = 15000 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
392 5 3 6 3.8 CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nnc(-c3ccccc3)[nH]2)c1O
CHEMBL233551 cxcr2_human Human No 4.8 IC50 = 15000 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cells
303 2 3 5 1.9 CC[C@@H](C)NC1=NS(=O)(=O)c2cc(Cl)cc(O)c2N1
CHEMBL3935902 cxcr2_human Human No 6.8 IC50 = 153 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
513 11 4 11 2.6 COC(=O)CNCC(=O)c1cccc(Nc2c(NC(c3ccc(C)o3)C3CCCS3)c(=O)c2=O)c1O
CHEMBL3938406 cxcr2_human Human No 6.8 IC50 = 157 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the beta -arrestin recruitment after receptor activation type.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 beta -arrestin line results in the recruitment of beta -arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation.>>J. Immunol. 170: 2904-2911).In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with beta -arrestin 2, a beta -arrestin 2 recruitment test for CXCR2 or CXCR1 based on beta -galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the beta -arrestin recruitment after receptor activation type.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 beta -arrestin line results in the recruitment of beta -arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation.>>J. Immunol. 170: 2904-2911).In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with beta -arrestin 2, a beta -arrestin 2 recruitment test for CXCR2 or CXCR1 based on beta -galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
467 7 3 8 3.3 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)CCOCC2)o1
CHEMBL4082136 cxcr2_human Human No 6.8 IC50 = 158.5 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
377 3 3 5 3.1 CC1=CCC[C@H]1NC(=O)Nc1ccc(C#N)c(S(=O)(=O)C(C)(C)C)c1O
CHEMBL4100674 cxcr2_human Human Yes 6.8 IC50 = 158.5 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
414 4 3 5 3.2 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)[C@]2(C)CCOC2)c1O
CHEMBL4072677 cxcr2_human Human No 6.8 IC50 = 158.5 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
388 4 3 4 3.9 CC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)NC2CCCC2(C)C)c1O
CHEMBL3818216 cxcr2_human Human No 6.8 IC50 = 158.5 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
436 4 3 4 5.2 CC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)Nc2cccc(Cl)c2Cl)c1O
CHEMBL3818331 cxcr2_human Human No 6.8 IC50 = 158.5 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
489 5 3 5 4.7 CCN1CCC(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c2O)CC1
CHEMBL3819521 cxcr2_human Human No 6.8 IC50 = 158.5 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
491 4 3 5 4.9 CN1CCC(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(Cl)c3Cl)c2O)CC1
CHEMBL3403836 cxcr2_human Human No 6.8 IC50 = 158.5 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
436 8 3 7 3.2 C[C@H](CO)Nc1cc(NS(C)(=O)=O)nc(SCc2cccc(Cl)c2Cl)n1
CHEMBL3403838 cxcr2_human Human No 6.8 IC50 = 158.5 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
396 10 3 7 2.7 CCCS(=O)(=O)Nc1cc(N[C@H](C)CO)nc(SCc2ccccc2)n1
CHEMBL4084545 cxcr2_human Human No 5.8 IC50 = 1584.9 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
404 5 3 5 3.3 COC1CCCCC1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)C)c1O
CHEMBL245182 cxcr2_human Human No 5.8 IC50 = 1584.9 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
455 10 3 9 3.3 CCN(CC)c1nc2nc(SCc3cccc(F)c3F)nc(NC(CO)CO)c2s1
CHEMBL3817880 cxcr2_human Human No 4.8 IC50 = 15848.9 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
507 4 3 5 4.8 C[C@H]1CN(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(Cl)c3Cl)c2O)C[C@@H](C)O1
CHEMBL3658247 cxcr2_human Human No 5.8 IC50 = 1585 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
426 7 1 6 4.4 O=C(Nc1ccc(F)cc1)c1ccc(SCCOc2cccc3c2OCCO3)nc1
CHEMBL387136 cxcr2_human Human No 7.8 IC50 = 16 nM Bind
Displacement of [125I]IL8 from CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR2 expressed in CHO cells
626 9 5 7 4.5 CCC(CC)(NS(=O)(=O)c1c(Cl)ccc(N/C(=N/C#N)Nc2ccccc2Br)c1O)N1CCC[C@@H]1C(=O)O
CHEMBL403656 cxcr2_human Human No 7.8 IC50 = 16 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
403 6 3 7 2.6 C[C@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2[nH]c(=O)c(C#N)cc12
CHEMBL3913959 cxcr2_human Human No 7.8 IC50 = 16 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
525 8 3 9 3.6 Cc1ccc(C(Nc2c(Nc3ccc(Cl)c(S(=O)(=O)N(C)C)c3O)c(=O)c2=O)C2CCCS2)o1
CHEMBL3658278 cxcr2_human Human No 7.8 IC50 = 16 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
445 7 1 6 5.0 O=C(CSc1ccc(C(=O)Nc2ccc(F)cc2)cn1)c1ccc(Cl)c([N+](=O)[O-])c1
CHEMBL253707 cxcr2_human Human No 7.8 IC50 = 16.5 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
461 7 3 7 3.4 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1occc1Br
CHEMBL404088 cxcr2_human Human No 6.8 IC50 = 160 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
429 7 2 5 3.3 COc1cc2[nH]c(-c3ccc(F)cc3)c(CCCC(=O)NS(C)(=O)=O)c2cc1C#N
CHEMBL3310775 cxcr2_human Human No 5.8 IC50 = 1600 nM Funct
Antagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assayAntagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assay
413 6 1 6 5.1 CC(C)Oc1ccc(-c2nc(SCc3cccc(F)c3F)nc(O)c2C#N)cc1
CHEMBL4787874 cxcr2_human Human No 5.8 IC50 = 1600 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
418 4 2 5 4.8 C[C@@H](NC(=S)Nc1sc2c(c1C(=O)OC(C)(C)C)CCOC2)c1ccccc1
CHEMBL4798569 cxcr2_human Human No 5.8 IC50 = 1600 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
474 4 2 6 5.5 CC(C)(C)OC(=O)c1c(NC(=S)Nc2ccc(OC(F)(F)F)cc2)sc2c1CCOC2
CHEMBL397869 cxcr2_human Human No 5.8 IC50 = 1600 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cells
419 1 3 5 3.5 O=S1(=O)N=C(Nc2c(F)cccc2Br)Nc2c(O)cc(Cl)cc21
CHEMBL3342303 cxcr2_human Human No 5.8 IC50 = 1610 nM Funct
Antagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assay
406 5 1 3 6.1 O=C(Nc1ccc(F)cc1)c1ccc(SCc2ccc(Cl)c(Cl)c2)nc1
CHEMBL3342303 cxcr2_human Human No 5.8 IC50 = 1610 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
406 5 1 3 6.1 O=C(Nc1ccc(F)cc1)c1ccc(SCc2ccc(Cl)c(Cl)c2)nc1
CHEMBL3658343 cxcr2_human Human No 6.8 IC50 = 166 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
417 6 3 6 2.5 O=C(Nc1ccc(F)cn1)c1cnc(SCc2ccccc2B(O)O)c(Cl)c1
CHEMBL3645135 cxcr2_human Human No 5.8 IC50 = 1670 nM Funct
Calcium Fluorescence Assay (FLIPR) : CXCR2 inhibition using calcium fluorescence assay (FLIPR).Calcium Fluorescence Assay (FLIPR) : CXCR2 inhibition using calcium fluorescence assay (FLIPR).
399 6 2 2 4.8 CC(C)(NC(=O)c1ccc2ccccc2c1C#CCCCc1ccccc1)C(=O)O
CHEMBL4472754 cxcr2_human Human No 7.8 IC50 = 17 nM Bind
Antagonist activity at CXCR2 (unknown origin)Antagonist activity at CXCR2 (unknown origin)
546 8 3 10 2.6 Cc1ccc([C@H](Nc2c(Nc3cccc(S(=O)(=O)N4CCN(C)CC4)c3O)c(=O)c2=O)[C@H]2CCCS2)o1
CHEMBL220860 cxcr2_human Human No 7.8 IC50 = 17 nM Bind
Displacement of [125I]IL8 from CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR2 expressed in CHO cells
407 4 3 5 3.0 Cc1ccccc1N/C(=N\C#N)Nc1ccc(Cl)c(S(=O)(=O)N(C)C)c1O
CHEMBL373522 cxcr2_human Human No 7.8 IC50 = 17 nM Bind
Displacement of [125I]IL8 from CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR2 expressed in CHO cells
562 8 4 7 4.6 CCC(CC)(NS(=O)(=O)c1c(Cl)ccc(N/C(=N/C#N)Nc2ccccc2C)c1O)N1C[C@H](C)O[C@H](C)C1
CHEMBL1162935 cxcr2_human Human No 7.8 IC50 = 17 nM Bind
Displacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cells
379 6 3 6 2.6 C[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccccc1
CHEMBL3952996 cxcr2_human Human No 7.8 IC50 = 17 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
580 8 3 10 3.3 Cc1ccc(C(Nc2c(Nc3ccc(Cl)c(S(=O)(=O)N4CCN(C)CC4)c3O)c(=O)c2=O)C2CCCS2)o1
CHEMBL404250 cxcr2_human Human No 7.8 IC50 = 17.2 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
451 7 3 7 3.6 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(C(F)(F)F)o1
CHEMBL3342312 cxcr2_human Human No 6.8 IC50 = 170 nM Funct
Antagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assay
406 6 2 6 3.9 O=C(Nc1ccc(F)cc1)c1ccc(SCc2ccccc2-c2nn[nH]n2)nc1
CHEMBL255481 cxcr2_human Human No 6.8 IC50 = 170 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
452 6 2 3 4.1 CS(=O)(=O)NC(=O)CCCc1c(-c2ccc(F)cc2)[nH]c2ccc(Br)cc12
CHEMBL3980279 cxcr2_human Human No 6.8 IC50 = 170 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
435 7 3 7 2.8 CN(C)C(=O)c1cccc(Nc2c(NC(c3ccccc3)C3CCCO3)c(=O)c2=O)c1O
CHEMBL315588 cxcr2_human Human No 6.8 IC50 = 170 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
427 5 1 5 6.4 Sc1nc(-c2ccc(Cl)cc2Cl)nn1Cc1cccc(Oc2ccccc2)c1
CHEMBL3310782 cxcr2_human Human No 5.8 IC50 = 1700 nM Funct
Antagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assayAntagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assay
333 4 1 5 3.9 N#Cc1c(O)nc(SCc2cccc(F)c2F)nc1C1CCC1
CHEMBL4795943 cxcr2_human Human No 5.8 IC50 = 1700 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
404 3 2 5 5.1 CC1COCc2sc(NC(=S)Nc3ccccc3)c(C(=O)OC(C)(C)C)c21
CHEMBL3104911 cxcr2_human Human No 5.8 IC50 = 1700 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
416 5 1 6 5.0 Oc1cc(CSc2cccc(Cl)c2Cl)nc2nc(Cc3ccccc3)nn12
CHEMBL3104913 cxcr2_human Human No 5.8 IC50 = 1700 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
384 5 1 6 4.0 Oc1cc(CSc2ccc(F)c(F)c2)nc2nc(Cc3ccccc3)nn12
CHEMBL3105083 cxcr2_human Human No 5.8 IC50 = 1700 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
347 3 1 5 3.9 Oc1cc(CSc2cccc(F)c2F)nc2c3c(nn12)CCCC3
CHEMBL254773 cxcr2_rabit Rabbit No 5.8 IC50 = 1700 nM Funct
Antagonist activity at rabbit CXCR2 by neutrophil chemotaxis assayAntagonist activity at rabbit CXCR2 by neutrophil chemotaxis assay
515 6 3 3 5.0 O=C(NCCc1c(-c2ccc(F)cc2)[nH]c2ccc(Br)cc12)NS(=O)(=O)c1ccccc1
CHEMBL3654439 cxcr2_human Human No 5.8 IC50 = 1700 nM Funct
Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.
399 8 2 5 4.0 CC(C)(NC(=O)c1ccc2sccc2c1OCCOc1ccccc1)C(=O)O
CHEMBL424887 cxcr2_human Human No 6.8 IC50 = 171 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells
359 3 3 7 0.7 CN(C)C(=O)c1cccc(/N=c2\c(O)c(O)\c2=N/C2CCOCC2)c1O
CHEMBL253255 cxcr2_human Human No 6.8 IC50 = 171 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
454 8 3 8 2.3 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(C(=O)N(C)C)o1
CHEMBL393452 cxcr2_human Human No 5.8 IC50 = 1720 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
294 4 3 5 2.8 Cc1cccc(O)c1Nc1c(Nc2ccccc2)c(=O)c1=O
CHEMBL3342312 cxcr2_human Human No 6.8 IC50 = 173 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
406 6 2 6 3.9 O=C(Nc1ccc(F)cc1)c1ccc(SCc2ccccc2-c2nn[nH]n2)nc1
CHEMBL4106677 cxcr2_human Human No 6.8 IC50 = 176 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
439 7 3 8 2.7 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)[C@H]2CCCO2)o1
CHEMBL3645130 cxcr2_human Human No 5.8 IC50 = 1760 nM Funct
Calcium Fluorescence Assay (FLIPR) : CXCR2 inhibition using calcium fluorescence assay (FLIPR).Calcium Fluorescence Assay (FLIPR) : CXCR2 inhibition using calcium fluorescence assay (FLIPR).
399 8 2 5 4.0 CC(C)(NC(=O)c1sc2ccccc2c1OCCOc1ccccc1)C(=O)O
CHEMBL1188997 cxcr2_human Human No 7.8 IC50 = 18 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
544 7 3 8 3.8 O=c1c(Nc2ccccc2)c(Nc2ccc(Cl)c(S(=O)(=O)N3CCC(N4CCCCC4)CC3)c2O)c1=O
CHEMBL537883 cxcr2_human Human No 7.8 IC50 = 18 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
544 7 3 8 3.8 O=c1c(Nc2ccccc2)c(Nc2ccc(Cl)c(S(=O)(=O)N3CCC(N4CCCCC4)CC3)c2O)c1=O
CHEMBL4777868 cxcr2_human Human No 5.8 IC50 = 1800 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
388 3 2 4 5.4 CC(C)(C)OC(=O)c1c(NC(=S)Nc2ccccc2)sc2c1CCCC2
CHEMBL3658312 cxcr2_human Human No 5.7 IC50 = 1810 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
422 6 1 5 5.7 O=C(Nc1ccc(F)cc1)c1ccc(SCC(=O)c2cc3ccccc3s2)nc1
CHEMBL3658277 cxcr2_human Human No 5.7 IC50 = 1850 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
434 6 1 4 5.8 O=C(CSc1ccc(C(=O)Nc2ccc(F)cc2)cn1)c1ccc(Cl)c(Cl)c1
CHEMBL577075 cxcr2_human Human No 5.7 IC50 = 1860 nM Bind
Displacement of [125I]IL-8 from human CXCR2 expressed in mouse BaF3 cells by liquid scintillation countingDisplacement of [125I]IL-8 from human CXCR2 expressed in mouse BaF3 cells by liquid scintillation counting
346 7 3 7 1.1 CCN(CC)Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O
CHEMBL403084 cxcr2_human Human No 7.7 IC50 = 19 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
413 6 2 4 3.6 Cc1cc2[nH]c(-c3ccc(F)cc3)c(CCCC(=O)NS(C)(=O)=O)c2cc1C#N
CHEMBL214047 cxcr2_human Human No 7.7 IC50 = 19.1 nM Funct
Inhibition of chemotaxis of CHO cells expressing human CXCR2Inhibition of chemotaxis of CHO cells expressing human CXCR2
345 5 3 6 1.7 CCC(CC)/N=c1\c(O)c(O)\c1=N/c1cccc(C(=O)N(C)C)c1O
CHEMBL3355238 cxcr2_human Human No 7.7 IC50 = 20.0 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
411 5 3 6 3.7 CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nc(=O)cc(C3CCCC3)[nH]2)c1O
CHEMBL396043 cxcr2_human Human No 7.7 IC50 = 20.0 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
423 8 3 8 4.0 C[C@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2nc(NC3CC3)sc12
CHEMBL4787966 cxcr2_human Human No 5.7 IC50 = 1900 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
454 4 2 6 5.5 CCOC(=O)c1c(NC(=S)Nc2ccc3c(c2)OC(F)(F)O3)sc2c1C(C)CCC2
CHEMBL3658323 cxcr2_human Human No 6.7 IC50 = 194 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
424 6 1 6 4.2 O=C(CSc1ccc(C(=O)Nc2ccc(F)cc2)cn1)c1ccc2c(c1)OCCO2
CHEMBL3891755 cxcr2_human Human No 6.7 IC50 = 195 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
541 8 2 9 3.9 COC(=O)[C@@H]1CCCN1C(=O)c1cccc(Nc2c(NC(c3ccc(C)o3)[C@H]3CCCS3)c(=O)c2=O)c1F
CHEMBL3426948 cxcr2_human Human No 5.7 IC50 = 1970 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
382 6 3 5 2.4 O=C(Nc1ccc(F)cc1)c1ccc(SCc2cccc(B(O)O)c2)nc1
CHEMBL3704563 cxcr2_human Human No 6.7 IC50 = 198 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
425 7 3 8 2.2 CN(C)C(=O)c1cccc(Nc2c(NC(c3ccco3)C3(C)COC3)c(=O)c2=O)c1O
CHEMBL3354834 cxcr2_human Human No 6.7 IC50 = 199.5 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
385 6 3 6 3.0 CCCc1cc(=O)nc(Nc2ccc(Cl)c(S(=O)(=O)C(C)C)c2O)[nH]1
CHEMBL4060060 cxcr2_human Human No 6.7 IC50 = 199.5 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
428 4 3 5 3.6 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2(C)CCCOC2)c1O
CHEMBL4066510 cxcr2_human Human No 6.7 IC50 = 199.5 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
428 4 3 5 3.6 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2(C)CCOCC2)c1O
CHEMBL4098979 cxcr2_human Human No 6.7 IC50 = 199.5 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
459 6 3 5 3.5 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2CCN(CCF)CC2)c1O
CHEMBL4084474 cxcr2_human Human No 6.7 IC50 = 199.5 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
374 4 3 4 3.5 CC1CCC(NC(=O)Nc2ccc(Cl)c(S(=O)(=O)C(C)C)c2O)C1
CHEMBL3342323 cxcr2_human Human No 5.7 IC50 = 1990 nM Funct
Antagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assay
440 8 3 6 1.9 O=C(O)CN(C(=O)c1ccc(SCc2ccccc2B(O)O)nc1)c1ccc(F)cc1
CHEMBL3342323 cxcr2_human Human No 5.7 IC50 = 1990 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
440 8 3 6 1.9 O=C(O)CN(C(=O)c1ccc(SCc2ccccc2B(O)O)nc1)c1ccc(F)cc1
CHEMBL3819382 cxcr2_human Human No 5.7 IC50 = 1995.3 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
490 5 3 5 3.8 CCN1CCN(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c2O)CC1
CHEMBL3819603 cxcr2_human Human No 5.7 IC50 = 1995.3 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
504 5 3 5 4.2 CC(C)N1CCN(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c2O)CC1
CHEMBL4465379 cxcr2_human Human No 8.7 IC50 = 2 nM Funct
Antagonist activity at CXCR2 (unknown origin) by [35S]-GTPgammaS binding assayAntagonist activity at CXCR2 (unknown origin) by [35S]-GTPgammaS binding assay
483 9 3 9 3.0 CC[C@@H](Nc1c(Nc2ccc(Cl)c(S(=O)(=O)N(C)OC)c2O)c(=O)c1=O)c1ccc(C)o1
CHEMBL4574181 cxcr2_human Human No 8.7 IC50 = 2 nM Bind
Displacement of [125I]IL-8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL-8 from human CXCR2 expressed in CHO cells
398 7 3 8 2.3 CC[C@@H](Nc1c(Nc2ccnc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(C)o1
CHEMBL211468 cxcr2_human Human No 8.7 IC50 = 2 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells
351 3 3 6 1.8 CN(C)C(=O)c1cccc(/N=c2\c(O)c(O)\c2=N/c2ccccc2)c1O
CHEMBL387431 cxcr2_human Human No 8.7 IC50 = 2 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells
385 3 3 6 2.5 CN(C)C(=O)c1cc(Cl)cc(/N=c2\c(O)c(O)\c2=N/c2ccccc2)c1O
CHEMBL271012 cxcr2_human Human No 8.7 IC50 = 2 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
366 6 3 7 2.6 C[C@H](CO)Nc1nc(SCc2ccccc2F)nc2[nH]c(=O)sc12
CHEMBL272105 cxcr2_human Human No 8.7 IC50 = 2 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
437 7 3 9 1.9 COC(=O)c1nc2c(N[C@H](C)CO)nc(SCc3cccc(F)c3F)nc2[nH]c1=O
CHEMBL401939 cxcr2_human Human No 8.7 IC50 = 2 nM Bind
Inhibition of CXCR2-mediated chemotaxis in Ba/F3 cells expressing human CXCR2Inhibition of CXCR2-mediated chemotaxis in Ba/F3 cells expressing human CXCR2
461 7 3 7 3.4 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(Br)co1
CHEMBL216602 cxcr2_human Human No 8.6 IC50 = 2.4 nM Funct
Inhibition of CXCL1-induced human neutrophil chemotaxisInhibition of CXCL1-induced human neutrophil chemotaxis
383 6 3 7 2.5 Cc1ccc([C@@H](C)Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)o1
CHEMBL4076676 cxcr2_human Human No 8.6 IC50 = 2.5 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
477 6 3 5 3.8 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2CCN(CC(F)F)CC2)c1O
CHEMBL3403851 cxcr2_human Human No 8.6 IC50 = 2.5 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
461 9 3 7 2.7 C[C@H](CO)Nc1cc(NS(=O)(=O)N2CCC2)nc(SCc2cccc(Cl)c2F)n1
CHEMBL216981 cxcr2_human Human Yes 8.6 IC50 = 2.6 nM Bind
Displacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cells
397 7 3 7 2.9 CC[C@H](c1ccc(o1)C)NC1=C(C(=O)C1=O)Nc1cccc(c1O)C(=O)N(C)C
CHEMBL427888 cxcr2_human Human No 8.6 IC50 = 2.8 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
413 8 4 8 2.1 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(CO)o1
CHEMBL1188821 cxcr2_human Human No 7.7 IC50 = 20 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
524 6 3 8 3.1 CN1CCCN(S(=O)(=O)c2c(Cl)ccc(Nc3c(Nc4ccccc4Cl)c(=O)c3=O)c2O)CC1
CHEMBL537441 cxcr2_human Human No 7.7 IC50 = 20 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
524 6 3 8 3.1 CN1CCCN(S(=O)(=O)c2c(Cl)ccc(Nc3c(Nc4ccccc4Cl)c(=O)c3=O)c2O)CC1
CHEMBL3904195 cxcr2_human Human No 7.7 IC50 = 20 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
513 9 3 10 2.9 COC(=O)CN(C)C(=O)c1cccc(Nc2c(N[C@@H](c3ccc(C)o3)C3CCCS3)c(=O)c2=O)c1O
CHEMBL25573 cxcr2_human Human No 6.7 IC50 = 200 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
253 2 3 3 2.9 N#Cc1ccc(NC(=O)Nc2ccccc2)c(O)c1
CHEMBL25573 cxcr2_human Human No 6.7 IC50 = 200 nM Bind
Inhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 2 expressed in CHO Cells using [125I]IL-8 radioligandInhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 2 expressed in CHO Cells using [125I]IL-8 radioligand
253 2 3 3 2.9 N#Cc1ccc(NC(=O)Nc2ccccc2)c(O)c1
CHEMBL4791845 cxcr2_human Human No 5.7 IC50 = 2000 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
442 4 2 4 6.2 CCOC(=O)c1c(NC(=S)Nc2ccc(C(F)(F)F)cc2)sc2c1C(C)CCC2
CHEMBL3654435 cxcr2_human Human No 5.7 IC50 = 2000 nM Funct
Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.
409 9 2 3 4.6 CC(C)(NC(=O)c1ccc2c(c1OCCCCc1ccccc1)CCCC2)C(=O)O
CHEMBL1437942 cxcr2_human Human No 5.7 IC50 = 2000 nM Bind
Displacement of [125I]GRO-alpha from human recombinant CXCR2 receptor expressed in CHO cellsDisplacement of [125I]GRO-alpha from human recombinant CXCR2 receptor expressed in CHO cells
271 3 1 5 3.0 Cc1cc2nc(CSc3ccccc3)cc(O)n2n1
CHEMBL86001 cxcr2_human Human No 5.7 IC50 = 2000 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
273 3 1 5 3.3 Sc1nc(-c2cccs2)nn1Cc1ccccc1
CHEMBL86002 cxcr2_human Human No 5.7 IC50 = 2000 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
335 3 1 4 4.6 Sc1nc(-c2cc(Cl)cc(Cl)c2)nn1Cc1ccccc1
CHEMBL3105087 cxcr2_human Human No 4.7 IC50 = 20000 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
321 4 1 5 3.6 CCc1cnn2c(O)cc(CSc3cccc(F)c3F)nc12
CHEMBL233552 cxcr2_human Human No 4.7 IC50 = 20000 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cells
315 1 3 5 2.0 O=S1(=O)N=C(NC2CCCC2)Nc2c(O)cc(Cl)cc21
CHEMBL392181 cxcr2_human Human No 6.7 IC50 = 205 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
294 4 3 5 2.8 Cc1ccc(Nc2c(Nc3ccccc3)c(=O)c2=O)c(O)c1
CHEMBL3704564 cxcr2_human Human No 6.7 IC50 = 207 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
439 7 3 8 2.5 Cc1coc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)COC2)c1
CHEMBL3426944 cxcr2_human Human Yes 7.7 IC50 = 21 nM Funct
Antagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysisAntagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysis
466 7 3 6 3.3 O=C(Nc1ccc(F)cc1)c1ccc(SCc2cc(OC(F)(F)F)ccc2B(O)O)nc1
CHEMBL3609016 cxcr2_human Human No 7.7 IC50 = 21 nM Funct
Antagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysisAntagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysis
446 8 3 7 2.3 O=C(Nc1ccc(F)cc1)c1ccc(N(Cc2ccc(B(O)O)cn2)Cc2ccco2)nc1
CHEMBL455431 cxcr2_human Human No 7.7 IC50 = 21 nM Bind
Displacement of [125I]CXCL1 from CXCR2 receptor in human PMN assessed as myeloperoxidase releaseDisplacement of [125I]CXCL1 from CXCR2 receptor in human PMN assessed as myeloperoxidase release
429 6 3 8 4.8 Cc1ccc([C@H](Nc2nsnc2Nc2cccc(C(=O)N(C)C)c2O)C(C)(C)C)o1
CHEMBL3901913 cxcr2_human Human No 7.7 IC50 = 21 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
539 8 3 10 3.5 COC(=O)[C@H]1CCCN1C(=O)c1cccc(Nc2c(NC(c3ccc(C)o3)C3CCCS3)c(=O)c2=O)c1O
CHEMBL253504 cxcr2_human Human No 7.7 IC50 = 21 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
433 7 3 7 3.7 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1sccc1Cl
CHEMBL3426944 cxcr2_human Human Yes 7.7 IC50 = 21 nM Bind
Inhibition of CXCR2 (unknown origin) transfected with RBL cellsInhibition of CXCR2 (unknown origin) transfected with RBL cells
466 7 3 6 3.3 O=C(Nc1ccc(F)cc1)c1ccc(SCc2cc(OC(F)(F)F)ccc2B(O)O)nc1
CHEMBL3342269 cxcr2_human Human Yes 6.7 IC50 = 210 nM Funct
Antagonist activity at human CXCR2 expressed in HEK293 cells assessed as inhibition of CXCL8-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at human CXCR2 expressed in HEK293 cells assessed as inhibition of CXCL8-induced intracellular Ca2+ release by fluorescence based calcium flux assay
382 6 3 5 2.4 Fc1ccc(cc1)NC(=O)c1ccc(nc1)SCc1ccccc1B(O)O
CHEMBL3658274 cxcr2_human Human No 6.7 IC50 = 210 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
400 6 1 4 5.1 O=C(CSc1ccc(C(=O)Nc2ccc(F)cc2)cn1)c1cccc(Cl)c1
CHEMBL4793810 cxcr2_human Human No 5.7 IC50 = 2100 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
392 4 2 4 5.3 CCOC(=O)c1c(NC(=S)Nc2ccc(F)cc2)sc2c1C(C)CCC2
CHEMBL440405 cxcr2_rabit Rabbit No 5.7 IC50 = 2100 nM Funct
Antagonist activity at rabbit CXCR2 by neutrophil chemotaxis assayAntagonist activity at rabbit CXCR2 by neutrophil chemotaxis assay
399 6 2 4 3.2 CS(=O)(=O)NC(=O)CCCc1c(-c2ccc(F)cc2)[nH]c2ccc(C#N)cc12
CHEMBL3654436 cxcr2_human Human No 5.7 IC50 = 2100 nM Funct
Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.Calcium Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes). A large fluorescence intensity increase is observed upon calcium association with Fluo-4. The dye is delivered to the cell interior using an acetoxymethylester form of Fluo-4, where the intracellular esterase activity results in the charged species being released and trapped within the cytoplasm of the cell. hence, influx of calcium to this cytoplasmic pocket, via release from intracellular pools and the phospholipase C cascade can be detected. By co-expressing the CXCR2 receptor and the promiscuous Galpha 16 protein, activation of this chemokine receptor is directed into this phospholipase C cascade resulting in intracellular calcium mobilization.The CHOK1 cells stably transfected with human CXCR2 and the promiscuous Galpha 16 protein were maintained in a log phase of growth at 37 C. and 5% CO2 in the following media: Iscove's.
411 9 2 4 4.0 CC(C)(NC(=O)c1ccc2c(c1OCCCOc1ccccc1)CCCC2)C(=O)O
CHEMBL3943808 cxcr2_human Human No 6.7 IC50 = 212 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the beta -arrestin recruitment after receptor activation type.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 beta -arrestin line results in the recruitment of beta -arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation.>>J. Immunol. 170: 2904-2911).In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with beta -arrestin 2, a beta -arrestin 2 recruitment test for CXCR2 or CXCR1 based on beta -galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the beta -arrestin recruitment after receptor activation type.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 beta -arrestin line results in the recruitment of beta -arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation.>>J. Immunol. 170: 2904-2911).In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with beta -arrestin 2, a beta -arrestin 2 recruitment test for CXCR2 or CXCR1 based on beta -galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
453 7 3 8 2.9 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2CCOCC2)o1
CHEMBL3342309 cxcr2_human Human No 5.7 IC50 = 2120 nM Funct
Antagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assay
382 6 2 4 4.5 O=C(O)c1cccc(CSc2ccc(C(=O)Nc3ccc(F)cc3)cn2)c1
CHEMBL3342309 cxcr2_human Human No 5.7 IC50 = 2120 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
382 6 2 4 4.5 O=C(O)c1cccc(CSc2ccc(C(=O)Nc3ccc(F)cc3)cn2)c1
CHEMBL3658260 cxcr2_human Human No 6.7 IC50 = 216 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
380 5 1 6 4.3 O=C(Nc1ccc(F)cc1)c1ccc(SCc2ccc3nonc3c2)nc1
CHEMBL4797191 cxcr2_human Human No 5.7 IC50 = 2190 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
425 4 3 6 3.0 CC(C)S(=O)(=O)c1c(Cl)ccc(NC2=NC(=O)C(c3ccc(F)cc3)N2)c1O
CHEMBL239767 cxcr2_human Human Yes 7.7 IC50 = 22 nM Bind
Binding affinity to CXCR2Binding affinity to CXCR2
351 3 3 4 3.7 O=C(Nc1ccccc1Br)Nc1ccc(cc1O)[N+](=O)[O-]
CHEMBL386072 cxcr2_human Human No 7.7 IC50 = 22 nM Bind
Displacement of [125I]IL8 from CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR2 expressed in CHO cells
611 8 5 7 4.4 CCC(CC)(NS(=O)(=O)c1c(Cl)ccc(N/C(=N/C#N)Nc2ccccc2Br)c1O)N1CCC(N)CC1
CHEMBL377397 cxcr2_human Human No 7.7 IC50 = 22 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells
337 3 4 6 1.5 CNC(=O)c1cccc(/N=c2\c(O)c(O)\c2=N/c2ccccc2)c1O
CHEMBL239767 cxcr2_human Human Yes 7.7 IC50 = 22 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
351 3 3 4 3.7 O=C(Nc1ccccc1Br)Nc1ccc(cc1O)[N+](=O)[O-]
CHEMBL379438 cxcr2_human Human No 7.7 IC50 = 22 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
325 4 3 7 2.2 O=c1c(O)c(Nc2ccc([N+](=O)[O-])cc2O)/c1=N/c1ccccc1
CHEMBL3426944 cxcr2_human Human Yes 7.7 IC50 = 22 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
466 7 3 6 3.3 O=C(Nc1ccc(F)cc1)c1ccc(SCc2cc(OC(F)(F)F)ccc2B(O)O)nc1
CHEMBL27446 cxcr2_human Human Yes 7.7 IC50 = 22 nM Bind
Inhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 2 expressed in CHO Cells using [125I]IL-8 radioligandInhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 2 expressed in CHO Cells using [125I]IL-8 radioligand
365 2 3 3 4.3 N#Cc1ccc(NC(=O)Nc2ccccc2Br)c(O)c1Cl
CHEMBL257025 cxcr2_human Human No 6.7 IC50 = 220 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
351 6 3 6 2.7 C[C@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2[nH]ncc12
CHEMBL255289 cxcr2_human Human No 6.7 IC50 = 220 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
427 7 2 4 4.0 CC(C)S(=O)(=O)NC(=O)CCCc1c(-c2ccc(F)cc2)[nH]c2ccc(C#N)cc12
CHEMBL4790233 cxcr2_human Human No 5.7 IC50 = 2200 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
458 5 2 5 6.1 CCOC(=O)c1c(NC(=S)Nc2ccc(OC(F)(F)F)cc2)sc2c1C(C)CCC2
CHEMBL3609004 cxcr2_human Human No 5.7 IC50 = 2200 nM Funct
Antagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysisAntagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysis
365 6 4 5 1.8 O=C(Nc1ccc(F)cc1)c1ccc(NCc2ccc(B(O)O)cc2)nc1
CHEMBL3648347 cxcr2_human Human No 5.7 IC50 = 2200 nM Funct
Calicum Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes).Calicum Fluorescence Assay: The assay is based on the detection of intracellular calcium changes detected by the selective, calcium-chelating dye, Fluo-4 (Molecular Probes).
507 8 2 3 6.6 CCC(NC(=O)c1ccc2ccccc2c1OCc1ccc(C(F)(F)F)cc1)(C(=O)O)c1ccccc1
CHEMBL3900726 cxcr2_human Human No 6.7 IC50 = 221 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
541 8 2 9 3.9 COC(=O)C1CCCN1C(=O)c1cccc(Nc2c(NC(c3ccc(C)o3)C3CCCS3)c(=O)c2=O)c1F
CHEMBL3658327 cxcr2_human Human No 5.7 IC50 = 2240 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
373 6 1 6 3.9 O=C(Nc1ccc(F)cc1)c1ccc(SCC(=O)c2ccsn2)nc1
CHEMBL3947915 cxcr2_human Human No 7.6 IC50 = 23 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
385 6 3 8 3.1 Cc1ccc(C(Nc2c(Nc3cccnc3O)c(=O)c2=O)C2CCCS2)o1
CHEMBL233961 cxcr2_human Human No 6.6 IC50 = 230 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cells
399 2 3 5 4.3 O=S1(=O)N=C(Nc2ccccc2-c2ccccc2)Nc2c(O)cc(Cl)cc21
CHEMBL4788391 cxcr2_human Human No 5.6 IC50 = 2300 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
390 3 2 5 4.6 CC(C)(C)OC(=O)c1c(NC(=S)Nc2ccccc2)sc2c1CCOC2
CHEMBL3609015 cxcr2_human Human No 5.6 IC50 = 2300 nM Funct
Antagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysisAntagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysis
464 8 3 7 2.0 O=C(Nc1ccc(F)cc1)c1ccc(N(Cc2ccc(B(O)O)cn2)CC2CCOCC2)nc1
CHEMBL312060 cxcr2_human Human No 5.6 IC50 = 2300 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
297 4 1 5 3.3 COc1ccc(-c2nc(S)n(Cc3ccccc3)n2)cc1
CHEMBL219347 cxcr2_human Human No 6.6 IC50 = 234 nM Bind
Displacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cells
393 7 3 6 3.0 CC[C@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccccc1
CHEMBL424694 cxcr2_human Human No 6.6 IC50 = 235 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
280 3 3 5 2.3 O=c1c(O)c(Nc2ccccc2)/c1=N/c1ccccc1O
CHEMBL385784 cxcr2_human Human No 6.6 IC50 = 236 nM Bind
Displacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cells
365 6 3 6 2.0 CN(C)C(=O)c1cccc(Nc2c(NCc3ccccc3)c(=O)c2=O)c1O
CHEMBL4777637 cxcr2_human Human No 4.6 IC50 = 23600 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
292 2 3 5 1.9 N#Cc1ccc(NC2=NC(=O)C(c3ccccc3)N2)c(O)c1
CHEMBL254568 cxcr2_human Human No 7.6 IC50 = 24 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
442 7 2 4 3.4 Cc1cc2[nH]c(-c3ccc(F)cc3)c(CCCC(=O)NS(=O)(=O)N(C)C)c2cc1C#N
CHEMBL4794294 cxcr2_human Human No 5.6 IC50 = 2400 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
418 4 2 5 4.8 C[C@H](NC(=S)Nc1sc2c(c1C(=O)OC(C)(C)C)CCOC2)c1ccccc1
CHEMBL234184 cxcr2_human Human No 5.6 IC50 = 2400 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cells
323 1 3 5 2.6 O=S1(=O)N=C(Nc2ccccc2)Nc2c(O)cc(Cl)cc21
CHEMBL85267 cxcr2_human Human No 5.6 IC50 = 2400 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
267 3 1 4 3.3 Sc1nc(-c2ccccc2)nn1Cc1ccccc1
CHEMBL219472 cxcr2_human Human No 6.6 IC50 = 244 nM Bind
Displacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cells
379 6 3 6 2.6 C[C@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccccc1
CHEMBL3704555 cxcr2_human Human No 6.6 IC50 = 244 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
453 7 3 8 2.8 Cc1cc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)COC2)oc1C
CHEMBL27863 cxcr2_human Human No 7.6 IC50 = 25 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
331 2 3 3 3.7 N#Cc1ccc(NC(=O)Nc2ccccc2Br)c(O)c1
CHEMBL3704565 cxcr2_human Human No 7.6 IC50 = 25 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
467 8 3 8 3.3 CC(C)c1coc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)COC2)c1
CHEMBL27863 cxcr2_human Human No 7.6 IC50 = 25 nM Bind
Inhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 2 expressed in CHO Cells using [125I]IL-8 radioligandInhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 2 expressed in CHO Cells using [125I]IL-8 radioligand
331 2 3 3 3.7 N#Cc1ccc(NC(=O)Nc2ccccc2Br)c(O)c1
CHEMBL3355247 cxcr2_human Human No 7.6 IC50 = 25.1 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
417 4 3 6 3.5 CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nc(=O)c(F)c(C(C)(C)C)[nH]2)c1O
CHEMBL4064083 cxcr2_human Human No 7.6 IC50 = 25.1 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
372 4 3 4 3.1 CC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)NC2CCC3CC32)c1O
CHEMBL4091344 cxcr2_human Human No 7.6 IC50 = 25.1 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
426 4 3 4 4.0 CC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)NC2CCC=C2C(F)(F)F)c1O
CHEMBL3818581 cxcr2_human Human No 7.6 IC50 = 25.1 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
543 4 3 5 5.9 CN1CCC2(CCC(S(=O)(=O)c3c(Cl)ccc(NC(=O)Nc4cccc(F)c4Cl)c3O)CC2)CC1
CHEMBL3818853 cxcr2_human Human No 7.6 IC50 = 25.1 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
446 4 3 4 5.2 O=C(Nc1ccc(Cl)c(S(=O)(=O)C2CCCC2)c1O)Nc1cccc(F)c1Cl
CHEMBL3819512 cxcr2_human Human Yes 7.6 IC50 = 25.1 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
475 4 3 5 4.4 CN1CCC(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c2O)CC1
CHEMBL3403843 cxcr2_human Human No 7.6 IC50 = 25.1 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
455 9 3 8 3.2 C[C@H](CO)Nc1cc(NS(=O)(=O)c2ccc(C#N)cc2)nc(SCc2ccccc2)n1
CHEMBL380732 cxcr2_human Human No 7.6 IC50 = 25.1 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
397 7 3 8 3.4 CC[C@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2nc(N)sc12
CHEMBL380947 cxcr2_human Human No 7.6 IC50 = 25.1 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
397 6 3 8 3.4 CC(C)(CO)Nc1nc(SCc2cccc(F)c2F)nc2nc(N)sc12
CHEMBL404661 cxcr2_human Human No 6.6 IC50 = 250 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
453 5 3 3 3.5 CS(=O)(=O)NC(=O)NCCc1c(-c2ccc(F)cc2)[nH]c2ccc(Br)cc12
CHEMBL233345 cxcr2_human Human No 6.6 IC50 = 250 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cells
353 2 3 6 2.6 COc1ccccc1NC1=NS(=O)(=O)c2cc(Cl)cc(O)c2N1
CHEMBL4786878 cxcr2_human Human No 5.6 IC50 = 2500 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
402 3 2 4 6.0 CC1CCCc2sc(NC(=S)Nc3ccccc3)c(C(=O)OC(C)(C)C)c21
CHEMBL4794114 cxcr2_human Human No 5.6 IC50 = 2500 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
435 5 3 3 5.9 CC1CCCc2sc(NC(=S)Nc3ccccc3)c(C(=O)NCc3ccccc3)c21
CHEMBL4527955 cxcr2_human Human No 5.6 IC50 = 2500 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in human U2OS cells cp-expressing betaarrestin-2/TEV protease and beta lactamase assessed as effect on beta-arrestin2 recruitment preincubated for 30 mins followed by IL-8 addition and further incubated for 5 hrs subsequently adding CCF4-AM staining and measured after 2 hrs by Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in human U2OS cells cp-expressing betaarrestin-2/TEV protease and beta lactamase assessed as effect on beta-arrestin2 recruitment preincubated for 30 mins followed by IL-8 addition and further incubated for 5 hrs subsequently adding CCF4-AM staining and measured after 2 hrs by Tango assay
464 5 2 3 6.3 C[C@@H](NC1=C(C(=O)Nc2ccc(Cl)c(C(F)(F)F)c2)C(=O)CC(C)(C)C1)c1ccccc1
CHEMBL3609009 cxcr2_human Human No 5.6 IC50 = 2500 nM Funct
Antagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysisAntagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysis
380 6 3 6 1.2 CN(Cc1cccc(B(O)O)c1)c1ncc(C(=O)Nc2ccc(F)cc2)cn1
CHEMBL257027 cxcr2_human Human No 5.6 IC50 = 2500 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
331 6 4 6 1.7 C[C@H](CO)Nc1nc(SCc2ccccc2)nc2[nH]c(=O)[nH]c12
CHEMBL4760919 cxcr2_human Human No 4.6 IC50 = 25000 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
421 5 3 6 2.7 CC(C)S(=O)(=O)c1c(Cl)ccc(NC2=NC(=O)[C@H](Cc3ccccc3)N2)c1O
CHEMBL241514 cxcr2_human Human Yes 4.6 IC50 = 25000 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
242 2 3 2 3.3 Cc1ccc(NC(=O)Nc2ccccc2)c(O)c1
CHEMBL3354833 cxcr2_human Human No 6.6 IC50 = 251.2 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
371 5 3 6 2.6 CCc1cc(=O)nc(Nc2ccc(Cl)c(S(=O)(=O)C(C)C)c2O)[nH]1
CHEMBL3355249 cxcr2_human Human No 6.6 IC50 = 251.2 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
413 4 3 6 3.7 Cc1c(C(C)(C)C)[nH]c(Nc2ccc(Cl)c(S(=O)(=O)C(C)C)c2O)nc1=O
CHEMBL4079718 cxcr2_human Human No 6.6 IC50 = 251.2 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
446 5 3 5 3.6 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2(CF)CCOCC2)c1O
CHEMBL4081963 cxcr2_human Human No 6.6 IC50 = 251.2 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
414 4 3 5 3.2 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2CCCOC2)c1O
CHEMBL4093397 cxcr2_human Human No 6.6 IC50 = 251.2 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
390 5 3 5 2.9 CO[C@@H]1CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)C)c1O
CHEMBL3818179 cxcr2_human Human No 6.6 IC50 = 251.2 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
477 4 3 5 4.5 CN1CC[C@H](S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(Cl)c3Cl)c2O)C1
CHEMBL3354825 cxcr2_human Human No 5.6 IC50 = 2511.9 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
383 4 3 6 2.5 CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nc(=O)c3c([nH]2)CCC3)c1O
CHEMBL3354829 cxcr2_human Human No 5.6 IC50 = 2511.9 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
409 5 3 7 3.3 CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nc(=O)cc(-c3ccco3)[nH]2)c1O
CHEMBL3354830 cxcr2_human Human No 5.6 IC50 = 2511.9 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
422 5 3 7 3.1 CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nc(=O)cc(-c3cccn3C)[nH]2)c1O
CHEMBL3355245 cxcr2_human Human No 5.6 IC50 = 2511.9 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
387 6 3 7 2.2 COCc1cc(=O)nc(Nc2ccc(Cl)c(S(=O)(=O)C(C)C)c2O)[nH]1
CHEMBL4068230 cxcr2_human Human No 5.6 IC50 = 2511.9 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
406 4 3 5 2.6 O=C(Nc1ccc(Cl)c(S(=O)(=O)C2COC2)c1O)N[C@H]1CCC=C1Cl
CHEMBL3645132 cxcr2_human Human No 5.6 IC50 = 2560 nM Funct
Calcium Fluorescence Assay (FLIPR) : CXCR2 inhibition using calcium fluorescence assay (FLIPR).Calcium Fluorescence Assay (FLIPR) : CXCR2 inhibition using calcium fluorescence assay (FLIPR).
435 10 2 4 4.9 CC(C)CC(C)(NC(=O)c1ccc2ccccc2c1OCCOc1ccccc1)C(=O)O
CHEMBL3701195 cxcr2_human Human No 6.6 IC50 = 257 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
475 8 3 9 2.1 Cc1ccc(C(Nc2c(Nc3cccc(S(=O)(=O)N(C)C)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL443583 cxcr2_human Human No 7.6 IC50 = 26 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cells
412 2 3 7 2.6 O=[N+]([O-])c1cc(O)c2c(c1)S(=O)(=O)N=C(Nc1ccccc1Br)N2
CHEMBL3704569 cxcr2_human Human No 7.6 IC50 = 26 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
507 8 3 8 3.5 Cc1ccc([C@H](Nc2c(Nc3cccc(C(=O)N(C)CC(F)(F)F)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL211468 cxcr2_human Human No 7.6 IC50 = 26 nM Funct
Inhibition of chemotaxis of CHO cells expressing human CXCR2Inhibition of chemotaxis of CHO cells expressing human CXCR2
351 3 3 6 1.8 CN(C)C(=O)c1cccc(/N=c2\c(O)c(O)\c2=N/c2ccccc2)c1O
CHEMBL3105084 cxcr2_human Human No 6.6 IC50 = 260 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
343 3 1 5 4.2 Oc1cc(CSc2cccc(F)c2F)nc2c3ccccc3nn12
CHEMBL257177 cxcr2_human Human No 6.6 IC50 = 260 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
461 7 2 4 4.7 N#Cc1ccc2[nH]c(-c3ccc(F)cc3)c(CCCC(=O)NS(=O)(=O)c3ccccc3)c2c1
CHEMBL402942 cxcr2_human Human No 6.6 IC50 = 260 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
458 10 3 5 2.8 COCCNS(=O)(=O)NC(=O)CCCc1c(-c2ccc(F)cc2)[nH]c2ccc(C#N)cc12
CHEMBL2178579 cxcr2_human Human Yes 6.6 IC50 = 260.7 nM Funct
Antagonist activity at CXCR2 assessed as inhibition of neutrophil CD11b up-regulationAntagonist activity at CXCR2 assessed as inhibition of neutrophil CD11b up-regulation
462 4 4 5 3.1 O=C(Nc1cccc(c1Cl)F)Nc1ccc(c(c1O)S(=O)(=O)N1CCNCC1)Cl
CHEMBL3609010 cxcr2_human Human No 5.6 IC50 = 2600 nM Funct
Antagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysisAntagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysis
366 6 4 6 1.2 O=C(Nc1ccc(F)cc1)c1cnc(NCc2ccc(B(O)O)cc2)nc1
CHEMBL3701191 cxcr2_human Human No 6.6 IC50 = 262 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
465 7 3 8 3.1 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N4CCCC4)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL4800297 cxcr2_human Human No 6.6 IC50 = 269 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
345 3 3 6 1.5 CC1NC(Nc2ccc(Cl)c(S(=O)(=O)C(C)C)c2O)=NC1=O
CHEMBL1185146 cxcr2_human Human No 7.6 IC50 = 27 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
406 5 3 7 1.9 CN1CCN(C(=O)c2cccc(Nc3c(Nc4ccccc4)c(=O)c3=O)c2O)CC1
CHEMBL392473 cxcr2_human Human No 7.6 IC50 = 27 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
406 5 3 7 1.9 CN1CCN(C(=O)c2cccc(Nc3c(Nc4ccccc4)c(=O)c3=O)c2O)CC1
CHEMBL370387 cxcr2_human Human Yes 6.6 IC50 = 270 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPADisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPA
326 3 2 7 2.9 Nc1nc2nc(SCc3cccc(F)c3F)nc(O)c2s1
CHEMBL4782078 cxcr2_human Human No 5.6 IC50 = 2700 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
421 4 3 3 6.2 CC1CCCc2sc(NC(=S)Nc3ccccc3)c(C(=O)Nc3ccccc3)c21
CHEMBL4782371 cxcr2_human Human No 5.6 IC50 = 2700 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
432 4 2 5 6.0 COc1cccc(NC(=S)Nc2sc3c(c2C(=O)OC(C)(C)C)C(C)CCC3)c1
CHEMBL4787532 cxcr2_human Human No 5.6 IC50 = 2700 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
388 4 2 4 5.6 CC(C)OC(=O)c1c(NC(=S)Nc2ccccc2)sc2c1C(C)CCC2
CHEMBL3913959 cxcr2_human Human No 6.6 IC50 = 272 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
525 8 3 9 3.6 Cc1ccc(C(Nc2c(Nc3ccc(Cl)c(S(=O)(=O)N(C)C)c3O)c(=O)c2=O)C2CCCS2)o1
CHEMBL3701183 cxcr2_human Human No 6.6 IC50 = 272 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
457 8 3 8 2.5 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(CF)COC2)o1
CHEMBL3951994 cxcr2_human Human No 6.6 IC50 = 273 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
455 7 3 8 3.4 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2CCCS2)o1
CHEMBL3342313 cxcr2_human Human No 6.6 IC50 = 275 nM Funct
Antagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assay
464 6 1 5 5.1 CC1(C)OB(c2ccccc2CSc2ccc(C(=O)Nc3ccc(F)cc3)cn2)OC1(C)C
CHEMBL3342313 cxcr2_human Human No 6.6 IC50 = 275 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
464 6 1 5 5.1 CC1(C)OB(c2ccccc2CSc2ccc(C(=O)Nc3ccc(F)cc3)cn2)OC1(C)C
CHEMBL239558 cxcr2_human Human No 6.6 IC50 = 276 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
253 2 3 3 2.9 N#Cc1cccc(NC(=O)Nc2ccccc2)c1O
CHEMBL3342304 cxcr2_human Human No 6.6 IC50 = 277 nM Funct
Antagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assay
354 5 2 4 4.5 O=C(Nc1ccc(F)cc1)c1ccc(SCc2ccccc2O)nc1
CHEMBL3342304 cxcr2_human Human No 6.6 IC50 = 277 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
354 5 2 4 4.5 O=C(Nc1ccc(F)cc1)c1ccc(SCc2ccccc2O)nc1
CHEMBL3342314 cxcr2_human Human No 6.6 IC50 = 278 nM Funct
Antagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assay
448 7 3 6 3.2 O=C(Nc1ccc(OC(F)(F)F)cc1)c1ccc(SCc2ccccc2B(O)O)nc1
CHEMBL3342314 cxcr2_human Human No 6.6 IC50 = 278 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
448 7 3 6 3.2 O=C(Nc1ccc(OC(F)(F)F)cc1)c1ccc(SCc2ccccc2B(O)O)nc1
CHEMBL399223 cxcr2_human Human No 7.6 IC50 = 28 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
489 5 3 6 4.1 O=C(c1c(Cl)ccc(Nc2c(Nc3ccccc3Br)c(=O)c2=O)c1O)N1CCCC1
CHEMBL3654441 cxcr2_human Human No 7.6 IC50 = 28 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
438 6 2 5 5.4 O=C(Nc1ccc(F)cc1)c1ccc(SCc2cc(OC(F)(F)F)ccc2O)nc1
CHEMBL3105081 cxcr2_human Human No 6.6 IC50 = 280 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
370 4 1 6 4.1 Oc1cc(CSc2cccc(F)c2F)nc2cc(-c3ccccn3)nn12
CHEMBL257659 cxcr2_human Human No 6.6 IC50 = 280 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
377 6 2 7 3.1 Cc1cnc2c(N[C@H](C)CO)nc(SCc3cccc(F)c3F)nc2n1
CHEMBL404057 cxcr2_human Human No 6.6 IC50 = 280 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
363 6 2 7 2.8 C[C@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2nccnc12
CHEMBL231710 cxcr2_human Human No 6.6 IC50 = 280 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cells
381 1 3 5 3.0 Cc1cc(O)c2c(c1)S(=O)(=O)N=C(Nc1ccccc1Br)N2
CHEMBL58619 cxcr2_human Human No 6.6 IC50 = 280 nM Bind
Evaluated using an SPA assay with recombinant human [125I]IL-8 and membranes prepared from Sf9 cells expressing human CXCR2Evaluated using an SPA assay with recombinant human [125I]IL-8 and membranes prepared from Sf9 cells expressing human CXCR2
386 5 1 4 2.7 O=C(Nc1ccc(F)cc1)c1ccc(S(=O)(=O)Cc2ccccc2)[n+]([O-])c1
CHEMBL4755486 cxcr2_human Human No 5.6 IC50 = 2800 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
373 5 3 6 2.3 CCC[C@@H]1NC(Nc2ccc(Cl)c(S(=O)(=O)C(C)C)c2O)=NC1=O
CHEMBL85872 cxcr2_human Human No 5.6 IC50 = 2800 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
335 3 1 4 4.3 FC(F)(F)c1ccc(-c2nc(S)n(Cc3ccccc3)n2)cc1
CHEMBL209121 cxcr2_human Human No 4.5 IC50 = 28600 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells
294 4 2 5 2.5 CN(c1ccccc1O)c1c(Nc2ccccc2)c(=O)c1=O
CHEMBL4746698 cxcr2_human Human No 7.5 IC50 = 29 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
373 5 3 6 2.3 CCC[C@H]1NC(Nc2ccc(Cl)c(S(=O)(=O)C(C)C)c2O)=NC1=O
CHEMBL221039 cxcr2_human Human No 7.5 IC50 = 29 nM Bind
Displacement of [125I]IL8 from CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR2 expressed in CHO cells
445 4 3 5 3.4 CN(C)S(=O)(=O)c1c(Cl)ccc(N/C(=N/C#N)Nc2cccc(Cl)c2F)c1O
CHEMBL3342319 cxcr2_human Human No 6.5 IC50 = 294 nM Funct
Antagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assay
383 6 3 6 1.8 O=C(Nc1ccc(F)cn1)c1ccc(SCc2ccccc2B(O)O)nc1
CHEMBL3963336 cxcr2_human Human No 6.5 IC50 = 294 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
541 8 2 9 3.9 COC(=O)[C@@H]1CCCN1C(=O)c1cccc(Nc2c(NC(c3ccc(C)o3)C3CCCS3)c(=O)c2=O)c1F
CHEMBL3342319 cxcr2_human Human No 6.5 IC50 = 294 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
383 6 3 6 1.8 O=C(Nc1ccc(F)cn1)c1ccc(SCc2ccccc2B(O)O)nc1
CHEMBL4765070 cxcr2_human Human No 4.5 IC50 = 29700 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
331 3 3 6 1.1 CC(C)S(=O)(=O)c1c(Cl)ccc(NC2=NC(=O)CN2)c1O
CHEMBL3609013 cxcr2_human Human No 6.5 IC50 = 298 nM Funct
Antagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysisAntagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysis
456 8 3 6 2.8 O=C(Nc1ccc(F)cc1)c1ccc(N(Cc2ccccc2)Cc2ccc(B(O)O)cn2)nc1
CHEMBL209859 cxcr2_human Human No 8.5 IC50 = 3 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells
305 3 3 6 2.2 N#Cc1ccc(Nc2c(O)c(=O)/c2=N\c2ccccc2)c(O)c1
CHEMBL429791 cxcr2_human Human No 8.5 IC50 = 3 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
399 6 3 8 3.5 C[C@H](CO)Nc1nc(SCc2cccc(Cl)c2F)nc2nc(N)sc12
CHEMBL4071499 cxcr2_human Human No 8.5 IC50 = 3.2 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
406 4 3 4 4.0 CC1=C(Cl)CCC1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)C)c1O
CHEMBL269707 cxcr2_human Human No 8.5 IC50 = 3.3 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
394 7 3 7 2.4 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccccn1
CHEMBL401940 cxcr2_human Human No 8.5 IC50 = 3.4 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
399 7 3 7 3.1 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccsc1
CHEMBL251811 cxcr2_human Human No 8.5 IC50 = 3.5 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
433 7 3 7 3.7 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc2ccccc2o1
CHEMBL401939 cxcr2_human Human No 8.5 IC50 = 3.5 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
461 7 3 7 3.4 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(Br)co1
CHEMBL216603 cxcr2_human Human No 8.4 IC50 = 3.6 nM Bind
Displacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cells
409 7 3 7 2.9 Cc1ccc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2CC2)o1
CHEMBL218115 cxcr2_human Human No 8.4 IC50 = 3.8 nM Bind
Displacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cells
383 7 3 7 2.6 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccco1
CHEMBL376414 cxcr2_human Human No 8.4 IC50 = 3.8 nM Bind
Displacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cells
425 6 3 7 3.5 Cc1ccc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C(C)(C)C)o1
CHEMBL253714 cxcr2_human Human No 8.4 IC50 = 3.8 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
417 7 3 7 3.2 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(Cl)co1
CHEMBL4089896 cxcr2_human Human No 8.4 IC50 = 4.0 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
422 5 4 5 3.0 CC(C)(CO)S(=O)(=O)c1c(Cl)ccc(NC(=O)N[C@@H]2CCC=C2Cl)c1O
CHEMBL4092148 cxcr2_human Human No 8.4 IC50 = 4.0 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
481 5 3 5 4.5 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2(C)CCN(C3CCC3)CC2)c1O
CHEMBL3819013 cxcr2_human Human No 8.4 IC50 = 4.0 nM Bind
Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubationAntagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation
491 4 3 5 4.3 C[C@H]1CN(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c2O)C[C@@H](C)O1
CHEMBL3403850 cxcr2_human Human No 8.4 IC50 = 4.0 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
445 9 3 7 2.2 C[C@H](CO)Nc1cc(NS(=O)(=O)N2CCC2)nc(SCc2cccc(F)c2F)n1
CHEMBL3403854 cxcr2_human Human No 8.4 IC50 = 4.0 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
475 9 3 8 1.8 C[C@H](CO)Nc1cc(NS(=O)(=O)N2CCOCC2)nc(SCc2cccc(F)c2F)n1
CHEMBL397237 cxcr2_human Human No 8.4 IC50 = 4.0 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
383 6 3 8 3.0 C[C@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2nc(N)sc12
CHEMBL397237 cxcr2_human Human No 8.4 IC50 = 4.0 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
383 6 3 8 3.0 C[C@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2nc(N)sc12
CHEMBL429791 cxcr2_human Human No 8.4 IC50 = 4.0 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
399 6 3 8 3.5 C[C@H](CO)Nc1nc(SCc2cccc(Cl)c2F)nc2nc(N)sc12
CHEMBL239767 cxcr2_human Human Yes 7.5 IC50 = 30 nM Funct
Antagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assay
351 3 3 4 3.7 O=C(Nc1ccccc1Br)Nc1ccc(cc1O)[N+](=O)[O-]
CHEMBL4473520 cxcr2_human Human No 7.5 IC50 = 30 nM Bind
Displacement of [125I]IL-8 from CXCR2 in human neutrophils incubated for 3 hrs by gamma counting methodDisplacement of [125I]IL-8 from CXCR2 in human neutrophils incubated for 3 hrs by gamma counting method
456 9 1 5 6.9 CCN(CC)CCCCNc1nc2cc(Cl)c(Cl)cc2nc1-c1cc2ccccc2o1
CHEMBL3901913 cxcr2_human Human No 7.5 IC50 = 30 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
539 8 3 10 3.5 COC(=O)[C@H]1CCCN1C(=O)c1cccc(Nc2c(NC(c3ccc(C)o3)C3CCCS3)c(=O)c2=O)c1O
CHEMBL3704573 cxcr2_human Human No 7.5 IC50 = 30 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
564 8 3 10 2.4 Cc1ccc([C@H](Nc2c(Nc3ccc(Cl)c(S(=O)(=O)N4CCN(C)CC4)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL315811 cxcr2_human Human No 6.5 IC50 = 300 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
369 3 1 4 5.2 Sc1nc(-c2ccc(Cl)cc2Cl)nn1Cc1ccc(Cl)cc1
CHEMBL4793669 cxcr2_human Human No 5.5 IC50 = 3000 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
404 5 2 5 5.2 CCOC(=O)c1c(NC(=S)Nc2cccc(OC)c2)sc2c1C(C)CCC2
CHEMBL257178 cxcr2_rabit Rabbit No 5.5 IC50 = 3000 nM Funct
Antagonist activity at rabbit CXCR2 by neutrophil chemotaxis assayAntagonist activity at rabbit CXCR2 by neutrophil chemotaxis assay
453 6 2 4 4.1 N#Cc1ccc2[nH]c(-c3ccc(F)cc3)c(CCCC(=O)NS(=O)(=O)C(F)(F)F)c2c1
CHEMBL231711 cxcr2_human Human No 5.5 IC50 = 3000 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cells
385 1 3 5 2.9 O=S1(=O)N=C(Nc2ccccc2Br)Nc2c(O)ccc(F)c21
CHEMBL4746803 cxcr2_human Human No 6.5 IC50 = 305 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
387 5 3 6 2.5 CC(C)CC1NC(Nc2ccc(Cl)c(S(=O)(=O)C(C)C)c2O)=NC1=O
CHEMBL4799848 cxcr2_human Human No 6.5 IC50 = 305 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
441 4 3 6 3.5 CC(C)S(=O)(=O)c1c(Cl)ccc(NC2=NC(=O)C(c3cccc(Cl)c3)N2)c1O
CHEMBL393248 cxcr2_human Human No 6.5 IC50 = 308 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
294 4 3 5 2.8 Cc1ccc(O)c(Nc2c(Nc3ccccc3)c(=O)c2=O)c1
CHEMBL3701196 cxcr2_human Human No 7.5 IC50 = 31 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
509 8 3 9 2.7 Cc1ccc(C(Nc2c(Nc3ccc(Cl)c(S(=O)(=O)N(C)C)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL3355239 cxcr2_human Human No 7.5 IC50 = 31.6 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
425 5 3 6 4.0 CC1CCCC1c1cc(=O)nc(Nc2ccc(Cl)c(S(=O)(=O)C(C)C)c2O)[nH]1
CHEMBL4070629 cxcr2_human Human No 7.5 IC50 = 31.6 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
460 6 3 5 4.0 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2(CCF)CCOCC2)c1O
CHEMBL3403834 cxcr2_human Human No 7.5 IC50 = 31.6 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
404 8 3 7 2.2 C[C@H](CO)Nc1cc(NS(C)(=O)=O)nc(SCc2cccc(F)c2F)n1
CHEMBL3403842 cxcr2_human Human No 7.5 IC50 = 31.6 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
464 9 3 7 4.0 C[C@H](CO)Nc1cc(NS(=O)(=O)c2ccc(Cl)cc2)nc(SCc2ccccc2)n1
CHEMBL3403846 cxcr2_human Human No 7.5 IC50 = 31.6 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
470 9 3 9 2.4 C[C@H](CO)Nc1cc(NS(=O)(=O)c2cn(C)cn2)nc(SCc2cccc(F)c2F)n1
CHEMBL233259 cxcr2_human Human No 7.5 IC50 = 31.6 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
381 6 3 8 3.4 C[C@H](CO)Nc1nc(SCc2ccccc2Cl)nc2nc(N)sc12
CHEMBL233263 cxcr2_human Human No 7.5 IC50 = 31.6 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
337 6 3 9 2.3 C[C@H](CO)Nc1nc(SCc2ccco2)nc2nc(N)sc12
CHEMBL245190 cxcr2_human Human No 7.5 IC50 = 31.6 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
399 7 4 9 2.0 Nc1nc2nc(SCc3cccc(F)c3F)nc(NC(CO)CO)c2s1
CHEMBL437013 cxcr2_human Human No 7.5 IC50 = 31.6 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
425 8 3 8 4.3 CC(C)Nc1nc2nc(SCc3cccc(F)c3F)nc(N[C@H](C)CO)c2s1
CHEMBL2178579 cxcr2_human Human Yes 6.5 IC50 = 310.5 nM Funct
Antagonist activity at CXCR2 assessed as inhibition of neutrophil shape changeAntagonist activity at CXCR2 assessed as inhibition of neutrophil shape change
462 4 4 5 3.1 O=C(Nc1cccc(c1Cl)F)Nc1ccc(c(c1O)S(=O)(=O)N1CCNCC1)Cl
CHEMBL4762597 cxcr2_human Human No 5.5 IC50 = 3100 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
345 3 3 6 1.5 CC(C)S(=O)(=O)c1c(Cl)ccc(NC2=NC(=O)[C@H](C)N2)c1O
CHEMBL379046 cxcr2_human Human No 5.5 IC50 = 3100 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells
324 3 4 6 1.8 O=C(O)c1ccc(/N=c2\c(O)c(O)\c2=N/c2ccccc2)c(O)c1
CHEMBL3658342 cxcr2_human Human No 5.5 IC50 = 3100 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
323 5 1 4 3.4 O=C(Nc1ccc(F)cn1)c1ccc(OCc2ccccc2)nc1
CHEMBL3704568 cxcr2_human Human No 6.5 IC50 = 311 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
393 6 3 8 2.7 Cc1ccc(C(Nc2c(Nc3cccc(C#N)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL3354824 cxcr2_human Human No 6.5 IC50 = 316.2 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
397 4 3 6 2.9 CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nc(=O)c3c([nH]2)CCCC3)c1O
CHEMBL4084135 cxcr2_human Human No 6.5 IC50 = 316.2 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
442 5 3 5 3.9 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)(C)[C@H]2CCOC2)c1O
CHEMBL4095602 cxcr2_human Human No 6.5 IC50 = 316.2 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
386 3 3 4 3.8 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)(C)C)c1O
CHEMBL4060778 cxcr2_human Human No 6.5 IC50 = 316.2 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
495 5 3 5 4.1 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C2CCN(CC(F)(F)F)CC2)c1O
CHEMBL4063949 cxcr2_human Human No 6.5 IC50 = 316.2 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
406 4 3 5 2.6 O=C(Nc1ccc(Cl)c(S(=O)(=O)C2COC2)c1O)N[C@@H]1CCC=C1Cl
CHEMBL4103634 cxcr2_human Human No 6.5 IC50 = 316.2 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
388 4 3 4 3.9 CC1CCCCC1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)C)c1O
CHEMBL3818917 cxcr2_human Human No 6.5 IC50 = 316.2 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
476 4 3 5 3.4 CN1CCN(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c2O)CC1
CHEMBL3819292 cxcr2_human Human Yes 6.5 IC50 = 316.2 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
409 3 4 4 3.6 NS(=O)(=O)c1c(Cl)ccc(NC(=O)Nc2cccc(Cl)c2Cl)c1O
CHEMBL3819013 cxcr2_human Human No 5.5 IC50 = 3162.3 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
491 4 3 5 4.3 C[C@H]1CN(S(=O)(=O)c2c(Cl)ccc(NC(=O)Nc3cccc(F)c3Cl)c2O)C[C@@H](C)O1
CHEMBL3403832 cxcr2_human Human No 5.5 IC50 = 3162.3 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
354 8 3 7 1.5 CS(=O)(=O)Nc1cc(NCCO)nc(SCc2ccccc2)n1
CHEMBL440405 cxcr2_human Human No 7.5 IC50 = 32 nM Funct
Antagonist activity at human cloned CXCR2 by calcium flux FLIPR assayAntagonist activity at human cloned CXCR2 by calcium flux FLIPR assay
399 6 2 4 3.2 CS(=O)(=O)NC(=O)CCCc1c(-c2ccc(F)cc2)[nH]c2ccc(C#N)cc12
CHEMBL431511 cxcr2_human Human No 7.5 IC50 = 32 nM Bind
Displacement of [125I]IL-8 from CHO cell membranes expressing human CX3C chemokine receptor 2Displacement of [125I]IL-8 from CHO cell membranes expressing human CX3C chemokine receptor 2
320 5 1 5 2.7 COC(=O)CSc1ccc(C(=O)Nc2ccc(F)cc2)cn1
CHEMBL240817 cxcr2_human Human No 7.5 IC50 = 32 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
305 4 3 6 2.3 N#Cc1cccc(Nc2c(Nc3ccccc3)c(=O)c2=O)c1O
CHEMBL441144 cxcr2_human Human No 7.5 IC50 = 32 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
392 4 3 5 3.9 O=c1c(Nc2ccc(Cl)cc2O)c(Nc2ccccc2Br)c1=O
CHEMBL57680 cxcr2_human Human No 7.5 IC50 = 32 nM Bind
Evaluated using an SPA assay with recombinant human [125I]IL-8 and membranes prepared from Sf9 cells expressing human CXCR2Evaluated using an SPA assay with recombinant human [125I]IL-8 and membranes prepared from Sf9 cells expressing human CXCR2
416 5 2 5 2.2 O=C(O)c1cccc(S(=O)(=O)c2ccc(C(=O)Nc3ccc(F)cc3)c[n+]2[O-])c1
CHEMBL3704564 cxcr2_human Human No 7.5 IC50 = 32 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
439 7 3 8 2.5 Cc1coc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)COC2)c1
CHEMBL3658341 cxcr2_human Human No 7.5 IC50 = 32 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
367 6 3 6 1.1 O=C(Nc1ccc(F)cn1)c1ccc(OCc2ccccc2B(O)O)nc1
CHEMBL3310785 cxcr2_human Human No 6.5 IC50 = 320 nM Funct
Antagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assayAntagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assay
391 6 1 7 3.3 CCOC(=O)[C@H]1C[C@@H]1c1nc(SCc2cccc(F)c2F)nc(O)c1C#N
CHEMBL3310794 cxcr2_human Human No 6.5 IC50 = 320 nM Funct
Antagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assayAntagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assay
294 4 1 4 3.6 Oc1cc(C2CC2)nc(SCc2cccc(F)c2F)n1
CHEMBL233346 cxcr2_human Human No 6.5 IC50 = 320 nM Funct
Antagonist activity at CXCR2 receptor expressed in CHOK1 cells assessed as human IL8-induced calcium mobilization by FLIPRAntagonist activity at CXCR2 receptor expressed in CHOK1 cells assessed as human IL8-induced calcium mobilization by FLIPR
415 3 3 6 4.4 O=S1(=O)N=C(Nc2ccccc2Oc2ccccc2)Nc2c(O)cc(Cl)cc21
CHEMBL280711 cxcr2_human Human Yes 6.5 IC50 = 320 nM Bind
Displacement of [125I]IL-8 from CXCR2 (unknown origin) stably expressed in CHO cellsDisplacement of [125I]IL-8 from CXCR2 (unknown origin) stably expressed in CHO cells
273 3 3 4 2.9 O=C(Nc1ccc(cc1O)[N+](=O)[O-])Nc1ccccc1
CHEMBL280711 cxcr2_human Human Yes 6.5 IC50 = 320 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
273 3 3 4 2.9 O=C(Nc1ccc(cc1O)[N+](=O)[O-])Nc1ccccc1
CHEMBL280711 cxcr2_human Human Yes 6.5 IC50 = 320 nM Bind
Inhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 2 expressed in CHO Cells using [125I]IL-8 radioligandInhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 2 expressed in CHO Cells using [125I]IL-8 radioligand
273 3 3 4 2.9 O=C(Nc1ccc(cc1O)[N+](=O)[O-])Nc1ccccc1
CHEMBL3311397 cxcr2_human Human No 5.5 IC50 = 3200 nM Funct
Antagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assayAntagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assay
420 4 1 4 4.2 Oc1nc(SCc2cccc(F)c2F)nc(C2CC2)c1I
CHEMBL3645134 cxcr2_human Human No 5.5 IC50 = 3230 nM Funct
Calcium Fluorescence Assay (FLIPR) : CXCR2 inhibition using calcium fluorescence assay (FLIPR).Calcium Fluorescence Assay (FLIPR) : CXCR2 inhibition using calcium fluorescence assay (FLIPR).
423 8 2 4 4.2 O=C(NC1(C(=O)O)CCC1)c1ccc2ccccc2c1OCCOc1ccc(F)cc1
CHEMBL576886 cxcr2_human Human No 5.5 IC50 = 3290 nM Bind
Displacement of [125I]IL-8 from human CXCR2 expressed in mouse BaF3 cells by liquid scintillation countingDisplacement of [125I]IL-8 from human CXCR2 expressed in mouse BaF3 cells by liquid scintillation counting
360 6 3 7 0.6 CCN(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)C(C)=O
CHEMBL3104912 cxcr2_human Human No 6.5 IC50 = 330 nM Bind
Displacement of [125I]GRO-alpha from human recombinant CXCR2 receptor expressed in CHO cellsDisplacement of [125I]GRO-alpha from human recombinant CXCR2 receptor expressed in CHO cells
384 5 1 6 4.0 Oc1cc(CSc2cccc(F)c2F)nc2nc(Cc3ccccc3)nn12
CHEMBL3701194 cxcr2_human Human No 6.5 IC50 = 335 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
369 6 3 8 2.2 Cc1ccc(C(Nc2c(Nc3cccnc3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL214286 cxcr2_human Human No 7.5 IC50 = 34 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells
323 3 4 6 1.2 NC(=O)c1cccc(/N=c2\c(O)c(O)\c2=N/c2ccccc2)c1O
CHEMBL4784641 cxcr2_human Human No 5.5 IC50 = 3400 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
450 5 2 7 4.6 COc1ccc(NC(=S)Nc2sc3c(c2C(=O)OC(C)(C)C)CCOC3)cc1OC
CHEMBL3701185 cxcr2_human Human No 6.5 IC50 = 341 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
481 7 4 9 2.0 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N4CC[C@@H](O)C4)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL3704558 cxcr2_human Human No 6.5 IC50 = 349 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
479 7 3 9 2.4 CN(C)C(=O)c1cccc(Nc2c(NC(c3ccc4c(c3)OCO4)C3(C)COC3)c(=O)c2=O)c1O
CHEMBL233263 cxcr2_human Human No 7.5 IC50 = 35 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
337 6 3 9 2.3 C[C@H](CO)Nc1nc(SCc2ccco2)nc2nc(N)sc12
CHEMBL3951994 cxcr2_human Human No 7.5 IC50 = 35 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
455 7 3 8 3.4 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2CCCS2)o1
CHEMBL3104912 cxcr2_human Human No 6.5 IC50 = 350 nM Funct
Antagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA methodAntagonist activity at human recombinant CXCR2 receptor expressed in CHO cells assessed as inhibition of IL8-induced [35S]GTPgammaS binding by SPA method
384 5 1 6 4.0 Oc1cc(CSc2cccc(F)c2F)nc2nc(Cc3ccccc3)nn12
CHEMBL257269 cxcr2_human Human No 6.5 IC50 = 350 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
378 6 3 6 2.7 C[C@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2[nH]c(=O)ccc12
CHEMBL203715 cxcr2_human Human No 6.5 IC50 = 350 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPADisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPA
453 9 3 9 4.9 CC[C@H](CO)Nc1nc(SCc2cccc(Oc3ccccc3)c2)nc2nc(N)sc12
CHEMBL3658245 cxcr2_human Human No 6.5 IC50 = 350 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
410 5 1 5 4.9 O=C(Nc1ccc(F)cc1)c1ccc(SCc2cccc3c2OCCCO3)nc1
CHEMBL313556 cxcr2_human Human No 6.5 IC50 = 350 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
345 3 1 4 4.0 Sc1nc(-c2ccccc2Br)nn1Cc1ccccc1
CHEMBL84753 cxcr2_human Human No 6.5 IC50 = 350 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
335 3 1 4 4.6 Sc1nc(-c2cccc(Cl)c2Cl)nn1Cc1ccccc1
CHEMBL312883 cxcr2_human Human No 5.5 IC50 = 3500 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
292 3 1 5 3.2 N#Cc1ccc(-c2nc(S)n(Cc3ccccc3)n2)cc1
CHEMBL84719 cxcr2_human Human No 5.5 IC50 = 3500 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
335 3 1 4 4.3 FC(F)(F)c1cccc(-c2nc(S)n(Cc3ccccc3)n2)c1
CHEMBL3342269 cxcr2_human Human Yes 6.5 IC50 = 356 nM Bind
Inhibition of CXCR2 (unknown origin) transfected with RBL cellsInhibition of CXCR2 (unknown origin) transfected with RBL cells
382 6 3 5 2.4 Fc1ccc(cc1)NC(=O)c1ccc(nc1)SCc1ccccc1B(O)O
CHEMBL239135 cxcr2_human Human No 6.5 IC50 = 358 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
325 5 3 7 2.4 O=c1c(Nc2ccccc2)c(Nc2c(O)cccc2[N+](=O)[O-])c1=O
CHEMBL510437 cxcr2_human Human No 7.4 IC50 = 36 nM Bind
Displacement of [125I]CXCL1 from CXCR2 receptor in human PMN assessed as myeloperoxidase releaseDisplacement of [125I]CXCL1 from CXCR2 receptor in human PMN assessed as myeloperoxidase release
415 7 3 8 4.4 Cc1ccc([C@H](Nc2nsnc2Nc2cccc(C(=O)N(C)C)c2O)C(C)C)o1
CHEMBL379438 cxcr2_human Human No 7.4 IC50 = 36 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells
325 4 3 7 2.2 O=c1c(O)c(Nc2ccc([N+](=O)[O-])cc2O)/c1=N/c1ccccc1
CHEMBL239136 cxcr2_human Human No 7.4 IC50 = 36 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
383 4 3 6 3.1 N#Cc1ccc(Nc2c(Nc3ccccc3Br)c(=O)c2=O)c(O)c1
CHEMBL234178 cxcr2_human Human No 6.4 IC50 = 360 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cells
385 1 3 5 2.9 O=S1(=O)N=C(Nc2ccccc2Br)Nc2c(O)cc(F)cc21
CHEMBL3658296 cxcr2_human Human No 5.4 IC50 = 3690 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
504 7 1 4 7.4 CCc1cc2c(cc1C(=O)CSc1ccc(C(=O)Nc3ccc(F)cc3)cn1)C(C)(C)CCC2(C)C
CHEMBL239348 cxcr2_human Human No 7.4 IC50 = 37 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in CHO cells
403 5 3 7 3.1 O=c1c(Nc2ccc([N+](=O)[O-])cc2O)c(Nc2ccccc2Br)c1=O
CHEMBL3915145 cxcr2_human Human No 7.4 IC50 = 37 nM Bind
In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).In Vitro Affinity Assay: â¿¿PathHunter HEK293-CXCR2⿝ or â¿¿U2OS hCXCR1 β-arrestin⿝ cells (DiscoveRx Corporation) were seeded overnight at 10 000 cells/well (384-well format) in 20 μl of Opti MEM I medium. A preincubation with the antagonist or the vehicle for 30 min at 37° C. and 5% CO2 was followed by 60 minutes of stimulation with CXCL8 at 37° C. and 5% CO2. The cells were then placed at ambient temperature for 30 minutes. The PathHunter detection reagent (DiscoveRx Corporation) was added. After incubation for 60 min at ambient temperature, the β-galactosidase induced by the luminescence during the β-arrestin-CXCR2 interaction was measured for 0.3 s in an Envision 2102 Multilabel Reader (PerkinElmer Life and Analytical Sciences).
539 8 3 10 3.5 COC(=O)[C@@H]1CCCN1C(=O)c1cccc(Nc2c(NC(c3ccc(C)o3)C3CCCS3)c(=O)c2=O)c1O
CHEMBL3701188 cxcr2_human Human No 7.4 IC50 = 37 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
523 8 3 10 2.6 COC(=O)[C@H]1CCCN1C(=O)c1cccc(Nc2c(N[C@@H](c3ccc(C)o3)C3(C)COC3)c(=O)c2=O)c1O
CHEMBL3658338 cxcr2_human Human No 7.4 IC50 = 37 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
398 6 4 6 2.2 O=C(Nc1ccc(F)cc1O)c1ccc(SCc2ccccc2B(O)O)nc1
CHEMBL3310769 cxcr2_human Human No 5.4 IC50 = 3700 nM Funct
Antagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assayAntagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assay
355 4 1 5 4.3 N#Cc1c(O)nc(SCc2cccc(F)c2F)nc1-c1ccccc1
CHEMBL3310784 cxcr2_human Human No 5.4 IC50 = 3700 nM Funct
Antagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assayAntagonist activity against human recombinant CXCR2 receptor expressed in CHO cell membranes by SPA based [35S]GTPgammaS binding assay
335 3 1 5 3.9 CC(C)(C)c1nc(SCc2cccc(F)c2F)nc(O)c1C#N
CHEMBL3704572 cxcr2_human Human No 6.4 IC50 = 373 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
473 7 3 8 3.2 Cc1ccc([C@H](Nc2c(Nc3ccc(Cl)c(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL3342269 cxcr2_human Human Yes 7.4 IC50 = 38 nM Funct
Antagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assay
382 6 3 5 2.4 Fc1ccc(cc1)NC(=O)c1ccc(nc1)SCc1ccccc1B(O)O
CHEMBL3342269 cxcr2_human Human Yes 7.4 IC50 = 38 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
382 6 3 5 2.4 Fc1ccc(cc1)NC(=O)c1ccc(nc1)SCc1ccccc1B(O)O
CHEMBL3426951 cxcr2_human Human No 6.4 IC50 = 387 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
396 7 3 5 2.5 O=C(Nc1ccc(F)cc1)c1ccc(SCCc2ccccc2B(O)O)nc1
CHEMBL4067429 cxcr2_human Human Yes 7.4 IC50 = 39.8 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
414 4 3 5 3.2 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)[C@@]2(C)CCOC2)c1O
CHEMBL4085657 cxcr2_human Human No 7.4 IC50 = 39.8 nM Bind
Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assayAntagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay
386 4 3 4 3.7 CC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)NC2CCCC23CC3)c1O
CHEMBL3819569 cxcr2_human Human No 7.4 IC50 = 39.8 nM Bind
Antagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader methodAntagonist activity at human recombinant CXCR2 assessed as inhibition of CXCL1-induced neutrophil chemotaxis after 45 mins by calcein-AM dye based plate reader method
434 3 3 4 5.1 CC(C)(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)Nc2cccc(F)c2Cl)c1O
CHEMBL3342291 cxcr2_human Human No 6.4 IC50 = 390 nM Funct
Antagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assay
338 5 1 3 4.8 O=C(Nc1ccc(F)cc1)c1ccc(SCc2ccccc2)nc1
CHEMBL233960 cxcr2_human Human No 6.4 IC50 = 390 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cells
337 1 3 5 2.9 Cc1ccccc1NC1=NS(=O)(=O)c2cc(Cl)cc(O)c2N1
CHEMBL4780042 cxcr2_human Human No 5.4 IC50 = 3900 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
417 5 2 5 5.2 CCOC(=O)c1c(NC(=S)Nc2ccc(N(C)C)cc2)sc2c1C(C)CCC2
CHEMBL3342270 cxcr2_human Human No 5.4 IC50 = 3900 nM Funct
Antagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at CXCR2 in human PMNs assessed as inhibition of CXCL1-induced intracellular Ca2+ release by fluorescence based calcium flux assay
330 5 2 6 2.3 O=C(Nc1ccc(F)cc1)c1ccc(SCc2nn[nH]n2)nc1
CHEMBL383235 cxcr2_human Human No 5.4 IC50 = 3900 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPADisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 membranes by SPA
361 7 3 8 3.1 CC[C@@H](CO)Nc1nc(SCc2ccccc2)nc2nc(N)sc12
CHEMBL234596 cxcr2_human Human No 5.4 IC50 = 3900 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR2 receptor expressed in CHO cells
419 1 3 5 3.5 O=S1(=O)N=C(Nc2cc(F)ccc2Br)Nc2c(O)cc(Cl)cc21
CHEMBL3342270 cxcr2_human Human No 5.4 IC50 = 3900 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
330 5 2 6 2.3 O=C(Nc1ccc(F)cc1)c1ccc(SCc2nn[nH]n2)nc1
CHEMBL3342291 cxcr2_human Human No 6.4 IC50 = 393 nM Bind
In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).In Vitro Inhibition Assay: An in vitro assay showed inhibition of CXCR2-mediated intracellular calcium release. Briefly, human neutrophils were suspended in HBSS- (without Ca2+ and Mg2+) containing 10 mM HEPES and FLIPR Calcium 3 dye (3.1x107 cells in total volume 1.7 mL). Cells were aliquoted (200 uL of the cell suspension per tube, 8 tubes total) and 2 uL of the designated compound (with appropriate dilutions) were added to each of 6 tubes. As controls, 2 uL of DMSO (1% final concentration) were added to 2 other tubes. Cells were incubated for 30 min at 37 C. After dye loading, tubes were centrifuged at 6,000 rpm for 1 min, supernatant was removed and the cell pellet was re-suspended in 200 uL of HBSS+ (with Ca2+ and Mg2+) containing 10 mM HEPES. The test compound or DMSO (control) was added again at the same concentrations that were used during cell loading. The cell suspension was aliquoted into a 96-well Reading Plate (Corning) in a volume of 90 uL (105 cells/well).
338 5 1 3 4.8 O=C(Nc1ccc(F)cc1)c1ccc(SCc2ccccc2)nc1
CHEMBL3701193 cxcr2_human Human No 6.4 IC50 = 394 nM Bind
In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
383 6 2 8 1.8 Cc1ccc(C(Nc2c(Nc3cccn(C)c3=O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL3354831 cxcr2_human Human No 6.4 IC50 = 398.1 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
433 6 3 6 3.6 CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nc(=O)cc(Cc3ccccc3)[nH]2)c1O
CHEMBL3355236 cxcr2_human Human No 6.4 IC50 = 398.1 nM Bind
Antagonist activity at CXCR2 (unknown origin) by beta-arrestin assayAntagonist activity at CXCR2 (unknown origin) by beta-arrestin assay
383 5 3 6 2.9 CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nc(=O)cc(C3CC3)[nH]2)c1O
CHEMBL4077201 cxcr2_human Human No 6.4 IC50 = 398.1 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
442 5 3 5 4.0 CCC1(S(=O)(=O)c2c(Cl)ccc(NC(=O)N[C@@H]3CCC=C3C)c2O)CCOCC1
CHEMBL4084077 cxcr2_human Human No 6.4 IC50 = 398.1 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
402 6 3 5 3.1 COCC(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)N[C@@H]2CCC=C2C)c1O
CHEMBL4088551 cxcr2_human Human No 6.4 IC50 = 398.1 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
456 5 3 5 4.3 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)C(C)(C)C2CCOCC2)c1O
CHEMBL3403828 cxcr2_human Human No 6.4 IC50 = 398.1 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
319 7 3 6 2.3 C[C@H](CO)Nc1cc(C(=O)O)nc(SCc2ccccc2)n1
CHEMBL3403833 cxcr2_human Human No 6.4 IC50 = 398.1 nM Bind
Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysisDisplacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis
382 9 3 7 2.3 CC[C@H](CO)Nc1cc(NS(C)(=O)=O)nc(SCc2ccccc2)n1
CHEMBL395342 cxcr2_human Human No 6.4 IC50 = 398.1 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPADisplacement of [125I]IL8 from human CXCR2 expressed in HEK 293 by SPA
439 9 2 8 4.3 CCN(CC)c1nc2nc(SCc3cccc(F)c3F)nc(N[C@H](C)CO)c2s1
CHEMBL3609018 cxcr2_human Human No 8.4 IC50 = 4 nM Funct
Antagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysisAntagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysis
457 8 3 7 2.2 O=C(Nc1ccc(F)cc1)c1cnc(N(Cc2ccccc2)Cc2ccc(B(O)O)cn2)nc1
CHEMBL254773 cxcr2_human Human No 8.4 IC50 = 4 nM Funct
Antagonist activity at human cloned CXCR2 by calcium flux FLIPR assayAntagonist activity at human cloned CXCR2 by calcium flux FLIPR assay
515 6 3 3 5.0 O=C(NCCc1c(-c2ccc(F)cc2)[nH]c2ccc(Br)cc12)NS(=O)(=O)c1ccccc1
CHEMBL375393 cxcr2_human Human No 8.4 IC50 = 4 nM Bind
Displacement of [125I]IL8 from CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR2 expressed in CHO cells
455 4 3 5 2.9 CN(C)S(=O)(=O)c1c(F)ccc(N/C(=N/C#N)Nc2ccccc2Br)c1O
CHEMBL397237 cxcr2_human Human No 8.4 IC50 = 4 nM Bind
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assayDisplacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
383 6 3 8 3.0 C[C@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2nc(N)sc12
CHEMBL252852 cxcr2_human Human No 8.4 IC50 = 4.1 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
411 8 3 7 3.2 CCc1ccc(C(CC)Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)o1
CHEMBL402986 cxcr2_human Human No 8.4 IC50 = 4.5 nM Bind
Displacement of [125I]-IL8 from human CXCR2 transfected in HEK293 cells after 4 hrs by microbeta counting analysisDisplacement of [125I]-IL8 from human CXCR2 transfected in HEK293 cells after 4 hrs by microbeta counting analysis
348 6 3 7 2.5 C[C@H](CO)Nc1nc(SCc2ccccc2)nc2[nH]c(=O)sc12
CHEMBL253497 cxcr2_human Human No 8.4 IC50 = 4.5 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
417 7 3 7 3.2 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(Cl)co1
CHEMBL269707 cxcr2_human Human No 8.4 IC50 = 4.5 nM Bind
Inhibition of CXCR2-mediated chemotaxis in Ba/F3 cells expressing human CXCR2Inhibition of CXCR2-mediated chemotaxis in Ba/F3 cells expressing human CXCR2
394 7 3 7 2.4 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccccn1
CHEMBL404490 cxcr2_human Human No 8.3 IC50 = 4.6 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
417 7 3 7 3.2 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(Cl)o1
CHEMBL253050 cxcr2_human Human No 8.3 IC50 = 4.7 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
461 7 3 7 3.4 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(Br)o1
CHEMBL253051 cxcr2_human Human No 8.3 IC50 = 4.8 nM Bind
Inhibition of CXCR2Inhibition of CXCR2
417 7 3 7 3.2 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(Cl)o1
CHEMBL401512 cxcr2_human Human No 8.3 IC50 = 4.9 nM Bind
Displacement of [125I]IL8 from human CXCR2 by SPA assayDisplacement of [125I]IL8 from human CXCR2 by SPA assay
411 7 3 6 3.1 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cccc(F)c1
CHEMBL401512 cxcr2_human Human No 8.3 IC50 = 4.9 nM Bind
Displacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR2 receptor expressed in BaF3 cells
411 7 3 6 3.1 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cccc(F)c1
CHEMBL4067429 cxcr2_human Human Yes 7.4 IC50 = 40 nM Bind
Antagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysisAntagonist activity at CXCR2 in human whole blood assessed as inhibition of GROalpha-stimulated CD11b upregulation preincubated for 15 mins followed by GROalpha stimulation measured after 15 mins by FITC-staining based FACS analysis
414 4 3 5 3.2 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)[C@@]2(C)CCOC2)c1O
CHEMBL239767 cxcr2_human Human Yes 7.4 IC50 = 40 nM Funct
Antagonist activity at human CXCR2 expressed in HEK293 cells assessed as inhibition of CXCL8-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at human CXCR2 expressed in HEK293 cells assessed as inhibition of CXCL8-induced intracellular Ca2+ release by fluorescence based calcium flux assay
351 3 3 4 3.7 O=C(Nc1ccccc1Br)Nc1ccc(cc1O)[N+](=O)[O-]
CHEMBL3310783 cxcr2_human Human Yes 7.4 IC50 = 40 nM Bind
Displacement of [125I]-GRO-alpha from human recombinant CXCR2 receptor expressed in CHO cell membranesDisplacement of [125I]-GRO-alpha from human recombinant CXCR2 receptor expressed in CHO cell membranes
319 4 1 5 3.5 N#Cc1c(O)nc(SCc2cccc(F)c2F)nc1C1CC1
CHEMBL393047 cxcr2_human Human No 6.4 IC50 = 400 nM Funct
Antagonist activity at CXCR2 receptor expressed in CHOK1 cells assessed as human IL8-induced calcium mobilization by FLIPRAntagonist activity at CXCR2 receptor expressed in CHOK1 cells assessed as human IL8-induced calcium mobilization by FLIPR
401 1 3 5 3.4 O=S1(=O)N=C(Nc2ccccc2Br)Nc2c(O)cc(Cl)cc21
CHEMBL404662 cxcr2_human Human No 6.4 IC50 = 400 nM Bind
Displacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assayDisplacement of europium labeled-human IL8 from human cloned CXCR2 expressed in Sf9 membrane with Galphai3-beta-1-gamma-2 by DELFIA binding assay
496 6 3 4 4.7 N#Cc1ccc2[nH]c(-c3ccc(F)cc3)c(CCNC(=O)NS(=O)(=O)c3ccccc3Cl)c2c1
CHEMBL61655 cxcr2_human Human No 6.4 IC50 = 400 nM Bind
Evaluated using an SPA assay with recombinant human [125I]IL-8 and membranes prepared from Sf9 cells expressing human CXCR2Evaluated using an SPA assay with recombinant human [125I]IL-8 and membranes prepared from Sf9 cells expressing human CXCR2
338 4 1 4 1.9 CC(C)S(=O)(=O)c1ccc(C(=O)Nc2ccc(F)cc2)c[n+]1[O-]
CHEMBL4745933 cxcr2_human Human No 5.4 IC50 = 4000 nM Funct
Antagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assayAntagonist activity in CXCR2 (unknown origin) expressed in human HEK293 cells co-expressing Galpha16 assessed as reduction in calcium immobilization pretreated with Fluo-4AM for 45 mins followed by compound addition and measured after 10 mins by Fluo-4AM dye based fluorescence assay
413 4 3 6 3.1 CC(C)S(=O)(=O)c1c(Cl)ccc(NC2=NC(=O)[C@H](C3CCCCC3)N2)c1O
CHEMBL211609 cxcr2_human Human No 7.4 IC50 = 41 nM Bind
Displacement of [125I]IL8 from human CXCR2 expressed in CHO cellsDisplacement of [125I]IL8 from human CXCR2 expressed in CHO cells
355 4 3 7 1.3 CN(C)C(=O)c1cccc(/N=c2\c(O)c(O)\c2=N/Cc2ccco2)c1O
CHEMBL3609003 cxcr2_human Human No 6.4 IC50 = 410 nM Funct
Antagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysisAntagonist activity at CXCR2 (unknown origin) transfected in RBL cells assessed as inhibition of IL-8-mediated intracellular calcium release preincubated for 30 mins followed by IL-8 addition by FLUO-4AM-based fluorescent microplate reader analysis
379 6 3 5 1.8 CN(Cc1cccc(B(O)O)c1)c1ccc(C(=O)Nc2ccc(F)cc2)cn1
CHEMBL85820 cxcr2_human Human No 6.4 IC50 = 410 nM Bind
Inhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranesInhibition of binding of [125I]IL8 to human recombinant CXC chemokine receptor 2 (CXCR2) expressed in HEK 293 membranes
335 3 1 4 4.6 Sc1nc(-c2ccc(Cl)cc2Cl)nn1Cc1ccccc1
CHEMBL4792599 cxcr2_human Human No 5.4 IC50 = 4100 nM Bind
Antagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assayAntagonist activity at CXCR2 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay