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
CHEMBL189475 cxcr1_human Human Yes 10.0 IC50 = 0.1 nM Bind
Inhibition of CXCR1 (unknown origin)Inhibition of CXCR1 (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 cxcr1_human Human Yes 10.0 IC50 = 0.1 nM Bind
Inhibition of CXCR1 (unknown origin)Inhibition of CXCR1 (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
CHEMBL191413 cxcr1_human Human Yes 9.0 IC50 = 1 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
283 5 1 3 2.1 CC(Cc1ccc(cc1)[C@H](C(=O)NS(=O)(=O)C)C)C
CHEMBL218665 cxcr1_human Human No 7.0 IC50 = 100 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 expressed in CHO cells
505 4 3 5 3.8 CN(C)S(=O)(=O)c1c(C(F)(F)F)ccc(N/C(=N/C#N)Nc2ccccc2Br)c1O
CHEMBL64391 cxcr1_human Human Yes 7.0 IC50 = 100 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
704 11 0 12 5.6 CCC(C)n1ncn(-c2ccc(N3CCN(c4ccc(OCC5COC(Cn6cncn6)(c6ccc(Cl)cc6Cl)O5)cc4)CC3)cc2)c1=O
CHEMBL253497 cxcr1_human Human No 7.0 IC50 = 100 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
417 7 3 7 3.2 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(Cl)co1
CHEMBL195433 cxcr1_human Human Yes 5.0 IC50 = 10000 nM Bind
Inhibition of C-X-C chemokine receptor type 1Inhibition of C-X-C chemokine receptor type 1
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 cxcr1_human Human No 5.0 IC50 = 10000 nM Bind
Inhibition of C-X-C chemokine receptor type 1Inhibition of C-X-C chemokine receptor type 1
505 7 2 6 4.7 Cn1nnnc1-c1cccc(NC(=O)N[C@@H]2CCCC[C@H]2CN2CCC[C@@H](Cc3ccc(F)cc3)C2)c1
CHEMBL104 cxcr1_human Human Yes 5.0 IC50 = 10000 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with centrifuged compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with centrifuged compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
344 4 0 2 5.4 Clc1ccccc1C(c1ccccc1)(c1ccccc1)n1ccnc1
CHEMBL4745933 cxcr1_human Human No 4.0 IC50 = 100000 nM Funct
Antagonist activity in CXCR1 (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 CXCR1 (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
CHEMBL4750465 cxcr1_human Human No 4.0 IC50 = 100000 nM Funct
Antagonist activity in CXCR1 (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 CXCR1 (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
CHEMBL4797191 cxcr1_human Human No 4.0 IC50 = 100000 nM Funct
Antagonist activity in CXCR1 (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 CXCR1 (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
CHEMBL253707 cxcr1_human Human No 6.0 IC50 = 1023 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
461 7 3 7 3.4 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1occc1Br
CHEMBL221481 cxcr1_human Human No 7.0 IC50 = 104 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 expressed in CHO cells
578 8 4 7 4.0 CCC(CC)(NS(=O)(=O)c1c(C)ccc(N/C(=N/C#N)Nc2ccccc2Br)c1O)N1CCOCC1
CHEMBL401940 cxcr1_human Human No 7.0 IC50 = 104 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
399 7 3 7 3.1 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccsc1
CHEMBL184882 cxcr1_human Human No 5.0 IC50 = 10500 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
396 7 0 6 3.6 CN1CCN(CCCOc2ccc(-c3nc(-c4ccc(F)cc4)no3)cc2)CC1
CHEMBL425882 cxcr1_human Human No 5.0 IC50 = 10600 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
294 5 0 4 3.9 CN(C)COc1ccc(-c2cc(-c3ccccc3)on2)cc1
CHEMBL3901913 cxcr1_human Human No 7.0 IC50 = 108 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
CHEMBL104 cxcr1_human Human Yes 5.0 IC50 = 10800 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with centrifuged compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with centrifuged compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
344 4 0 2 5.4 Clc1ccccc1C(c1ccccc1)(c1ccccc1)n1ccnc1
CHEMBL373522 cxcr1_human Human No 6.0 IC50 = 1082 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 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
CHEMBL3913959 cxcr1_human Human No 6.0 IC50 = 1096 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
CHEMBL376414 cxcr1_human Human No 8.0 IC50 = 11 nM Bind
Displacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR1 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
CHEMBL404060 cxcr1_human Human No 6.0 IC50 = 1110 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
433 7 3 7 3.7 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(Cl)s1
CHEMBL26830 cxcr1_human Human No 5.0 IC50 = 11100 nM Bind
Inhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligandInhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligand
365 2 3 3 4.3 N#Cc1c(Cl)ccc(NC(=O)Nc2ccccc2Br)c1O
CHEMBL3956601 cxcr1_human Human No 7.0 IC50 = 113 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).
489 7 3 8 4.0 Cc1ccc(C(Nc2c(Nc3ccc(Cl)c(C(=O)N(C)C)c3O)c(=O)c2=O)C2CCCS2)o1
CHEMBL3980279 cxcr1_human Human No 5.9 IC50 = 1148 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
CHEMBL3704573 cxcr1_human Human No 6.9 IC50 = 115 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
CHEMBL3701184 cxcr1_human Human No 5.9 IC50 = 1150 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
CHEMBL183537 cxcr1_human Human No 4.9 IC50 = 11500 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
350 5 0 6 3.0 CN1CCN(COc2ccc(-c3cc(-c4ccccn4)on3)cc2)CC1
CHEMBL3701196 cxcr1_human Human No 6.9 IC50 = 117 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
CHEMBL1034 cxcr1_human Human Yes 7.9 IC50 = 12 nM Bind
Inhibition of wild type CXCR1 transfected in mouse L1.2 cells assessed as inhibition of CXCL8-induced cell migration pretreated for 15 mins measured after 4 hrsInhibition of wild type CXCR1 transfected in mouse L1.2 cells assessed as inhibition of CXCL8-induced cell migration pretreated for 15 mins measured after 4 hrs
295 4 2 2 4.4 O=C(O)Cc1ccccc1Nc1c(Cl)cccc1Cl
CHEMBL139 cxcr1_human Human Yes 7.9 IC50 = 12 nM Bind
Inhibition of wild type CXCR1 transfected in mouse L1.2 cells assessed as inhibition of CXCL8-induced cell migration pretreated for 15 mins measured after 4 hrsInhibition of wild type CXCR1 transfected in mouse L1.2 cells assessed as inhibition of CXCL8-induced cell migration pretreated for 15 mins measured after 4 hrs
295 4 2 2 4.4 O=C(O)Cc1ccccc1Nc1c(Cl)cccc1Cl
CHEMBL231924 cxcr1_human Human No 4.9 IC50 = 12000 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR1 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR1 receptor expressed in CHO cells
368 2 3 7 2.5 O=[N+]([O-])c1cc(O)c2c(c1)S(=O)(=O)N=C(Nc1ccccc1Cl)N2
CHEMBL184401 cxcr1_human Human No 4.9 IC50 = 12100 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
339 6 0 6 3.8 CN(C)COc1ccc(-c2cc(-c3ccc([N+](=O)[O-])cc3)on2)cc1
CHEMBL3701191 cxcr1_human Human No 5.9 IC50 = 1300 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
CHEMBL393047 cxcr1_human Human No 4.9 IC50 = 13000 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR1 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR1 receptor expressed in CHO cells
401 1 3 5 3.4 O=S1(=O)N=C(Nc2ccccc2Br)Nc2c(O)cc(Cl)cc21
CHEMBL393253 cxcr1_human Human No 4.9 IC50 = 13000 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR1 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR1 receptor expressed in CHO cells
375 1 3 5 3.4 O=S1(=O)N=C(Nc2cccc(F)c2Cl)Nc2c(O)cc(Cl)cc21
CHEMBL4106677 cxcr1_human Human No 5.9 IC50 = 1322 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
CHEMBL185259 cxcr1_human Human No 4.9 IC50 = 13360 nM Bind
Concentration required to inhibit [125I]-IL-8 binding towards C-X-C chemokine receptor type 1 of human expressed in CHO cellsConcentration required to inhibit [125I]-IL-8 binding towards C-X-C chemokine receptor type 1 of human expressed in CHO cells
374 2 3 2 5.1 O=C(Nc1ccccc1Br)Nc1ccc(Cl)c(Cl)c1O
CHEMBL3609008 cxcr1_human Human No 5.9 IC50 = 1340 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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(NCc2cccc(B(O)O)c2)nc1
CHEMBL359670 cxcr1_human Human No 5.9 IC50 = 1366 nM Bind
Concentration required to inhibit [125I]-IL-8 binding towards C-X-C chemokine receptor type 1 of human expressed in CHO cellsConcentration required to inhibit [125I]-IL-8 binding towards C-X-C chemokine receptor type 1 of human expressed in CHO cells
419 3 4 4 3.1 NS(=O)(=O)c1c(Cl)ccc(NC(=O)Nc2ccccc2Br)c1O
CHEMBL253504 cxcr1_human Human No 5.9 IC50 = 1372 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
433 7 3 7 3.7 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1sccc1Cl
CHEMBL3609005 cxcr1_human Human No 5.9 IC50 = 1400 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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
CHEMBL455431 cxcr1_human Human No 6.8 IC50 = 143 nM Bind
Displacement of [125I]CXCL8 from CXCR1 receptor in human PMN assessed as myeloperoxidase releaseDisplacement of [125I]CXCL8 from CXCR1 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
CHEMBL3701195 cxcr1_human Human No 5.8 IC50 = 1442 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
CHEMBL220182 cxcr1_human Human No 6.8 IC50 = 145 nM Bind
Displacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cells
437 7 3 8 2.7 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc2c(c1)OCO2
CHEMBL4793352 cxcr1_human Human No 4.8 IC50 = 14700 nM Funct
Antagonist activity in CXCR1 (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 CXCR1 (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 CCCC1NC(Nc2ccc(Cl)c(S(=O)(=O)C(C)C)c2O)=NC1=O
CHEMBL269707 cxcr1_human Human No 6.8 IC50 = 148 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
394 7 3 7 2.4 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccccn1
CHEMBL253499 cxcr1_human Human No 6.8 IC50 = 150 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
459 8 3 7 4.3 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(-c2ccccc2)co1
CHEMBL27863 cxcr1_human Human No 4.8 IC50 = 15100 nM Bind
Inhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligandInhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligand
331 2 3 3 3.7 N#Cc1ccc(NC(=O)Nc2ccccc2Br)c(O)c1
CHEMBL3704555 cxcr1_human Human No 5.8 IC50 = 1541 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
CHEMBL220797 cxcr1_human Human No 5.8 IC50 = 1548 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 expressed in CHO cells
411 4 3 5 2.8 CN(C)S(=O)(=O)c1c(Cl)ccc(N/C(=N/C#N)Nc2ccccc2F)c1O
CHEMBL3951994 cxcr1_human Human No 5.8 IC50 = 1564 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
CHEMBL64391 cxcr1_human Human Yes 6.8 IC50 = 158.5 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
704 11 0 12 5.6 CCC(C)n1ncn(-c2ccc(N3CCN(c4ccc(OCC5COC(Cn6cncn6)(c6ccc(Cl)cc6Cl)O5)cc4)CC3)cc2)c1=O
CHEMBL3701183 cxcr1_human Human No 5.8 IC50 = 1595 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
CHEMBL216981 cxcr1_human Human Yes 6.8 IC50 = 160 nM Funct
Antagonist activity in CXCR1 (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 CXCR1 (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
CHEMBL184318 cxcr1_human Human No 5.8 IC50 = 1600 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
383 5 0 5 4.2 CN1CCN(COc2ccc(-c3cc(-c4ccc(Cl)cc4)on3)cc2)CC1
CHEMBL3704561 cxcr1_human Human No 5.8 IC50 = 1611 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
CHEMBL252898 cxcr1_human Human No 6.8 IC50 = 165 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
399 7 3 7 3.1 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccsc1
CHEMBL3609006 cxcr1_human Human No 5.8 IC50 = 1700 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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)cn1)c1ccc(C(=O)Nc2ccc(F)cc2)cn1
CHEMBL3609010 cxcr1_human Human No 5.8 IC50 = 1700 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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
CHEMBL3609012 cxcr1_human Human No 5.8 IC50 = 1700 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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
381 6 3 7 0.6 CN(Cc1ccc(B(O)O)cn1)c1ncc(C(=O)Nc2ccc(F)cc2)cn1
CHEMBL3704563 cxcr1_human Human No 5.8 IC50 = 1706 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
CHEMBL3915145 cxcr1_human Human No 6.8 IC50 = 171 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
CHEMBL253927 cxcr1_human Human No 6.8 IC50 = 171 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
398 7 3 8 2.3 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(C)on1
CHEMBL404059 cxcr1_human Human No 6.8 IC50 = 179 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
399 7 3 7 3.1 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cccs1
CHEMBL427888 cxcr1_human Human No 6.7 IC50 = 182 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
413 8 4 8 2.1 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(CO)o1
CHEMBL280711 cxcr1_human Human Yes 4.7 IC50 = 18200 nM Bind
Displacement of [125I]IL-8 from CXCR1 (unknown origin) stably expressed in CHO cellsDisplacement of [125I]IL-8 from CXCR1 (unknown origin) stably expressed in CHO cells
273 3 3 4 2.9 O=C(Nc1ccc(cc1O)[N+](=O)[O-])Nc1ccccc1
CHEMBL280711 cxcr1_human Human Yes 4.7 IC50 = 18200 nM Bind
Inhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligandInhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligand
273 3 3 4 2.9 O=C(Nc1ccc(cc1O)[N+](=O)[O-])Nc1ccccc1
CHEMBL376540 cxcr1_human Human No 6.7 IC50 = 187 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 expressed in CHO cells
451 4 3 5 3.1 Cc1ccc(N/C(=N/C#N)Nc2ccccc2Br)c(O)c1S(=O)(=O)N(C)C
CHEMBL386072 cxcr1_human Human No 6.7 IC50 = 188 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 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
CHEMBL3976863 cxcr1_human Human No 5.7 IC50 = 1892 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
CHEMBL375393 cxcr1_human Human No 6.7 IC50 = 192 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 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
CHEMBL401512 cxcr1_human Human No 6.7 IC50 = 197 nM Bind
Displacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR1 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
CHEMBL216981 cxcr1_human Human Yes 6.7 IC50 = 198.3 nM Funct
Antagonist activity at CXCR1 (unknown origin) expressed in HEK293 cells assessed as suppression of IL-8-induced inhibition of forskolin-induced cAMP formation preincubated for 15 mins followed by forskolin and IL-8 stimulation and measured after 15 mins by cAMP-d2 and Eu-Anti-cAMP based fluorescence assayAntagonist activity at CXCR1 (unknown origin) expressed in HEK293 cells assessed as suppression of IL-8-induced inhibition of forskolin-induced cAMP formation preincubated for 15 mins followed by forskolin and IL-8 stimulation and measured after 15 mins by cAMP-d2 and Eu-Anti-cAMP 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
CHEMBL216981 cxcr1_human Human Yes 6.7 IC50 = 198.3 nM Funct
Antagonist activity at CXCR1 (unknown origin) stably expressed in HEK293 cells assessed as reduction in IL-8-induced intracellular calcium change incubated for 15 mins followed by IL-8-stimulation and measured after 15 mins by cAMP-d2/Eu-Anti-cAM based fluorescence assayAntagonist activity at CXCR1 (unknown origin) stably expressed in HEK293 cells assessed as reduction in IL-8-induced intracellular calcium change incubated for 15 mins followed by IL-8-stimulation and measured after 15 mins by cAMP-d2/Eu-Anti-cAM 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
CHEMBL104 cxcr1_human Human Yes 5.7 IC50 = 1995.3 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
344 4 0 2 5.4 Clc1ccccc1C(c1ccccc1)(c1ccccc1)n1ccnc1
CHEMBL2324200 cxcr1_human Human No 5.7 IC50 = 1995.3 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
822 2 2 4 6.0 O=C1OC(c2cc(I)c(O)c(I)c2)(c2c(I)cc(O)cc2I)c2ccccc21
CHEMBL64391 cxcr1_human Human Yes 4.7 IC50 = 19952.6 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with Tween-80-treated compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with Tween-80-treated compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
704 11 0 12 5.6 CCC(C)n1ncn(-c2ccc(N3CCN(c4ccc(OCC5COC(Cn6cncn6)(c6ccc(Cl)cc6Cl)O5)cc4)CC3)cc2)c1=O
CHEMBL3913959 cxcr1_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).
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
CHEMBL104 cxcr1_human Human Yes 5.7 IC50 = 2000 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
344 4 0 2 5.4 Clc1ccccc1C(c1ccccc1)(c1ccccc1)n1ccnc1
CHEMBL183425 cxcr1_human Human No 5.7 IC50 = 2000 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
395 7 0 5 4.2 CN1CCN(CCCOc2ccc(-c3cc(-c4ccc(F)cc4)no3)cc2)CC1
CHEMBL501985 cxcr1_human Human No 4.7 IC50 = 20000 nM Bind
Displacement of [125I]IL8 from human recombinant IL8 type A receptorDisplacement of [125I]IL8 from human recombinant IL8 type A receptor
534 7 3 7 4.7 CC(=O)O[C@H]1C2=C([C@H](O)C[C@@]3(C)[C@H]2CC[C@@H]3[C@H](C)CCCC(C)C)[C@@]2(C)CC[C@H](O)C[C@]2(O)[C@H]1OC(C)=O
CHEMBL233346 cxcr1_human Human No 4.7 IC50 = 20000 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR1 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR1 receptor expressed in CHO cells
415 3 3 6 4.4 O=S1(=O)N=C(Nc2ccccc2Oc2ccccc2)Nc2c(O)cc(Cl)cc21
CHEMBL4746698 cxcr1_human Human No 4.7 IC50 = 20300 nM Funct
Antagonist activity in CXCR1 (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 CXCR1 (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
CHEMBL3609019 cxcr1_human Human No 5.7 IC50 = 2050 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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
458 8 3 8 1.5 O=C(Nc1ccc(F)cc1)c1cnc(N(Cc2ccccn2)Cc2ccc(B(O)O)cn2)nc1
CHEMBL3979652 cxcr1_human Human No 5.7 IC50 = 2075 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).
453 7 3 8 3.1 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)CCCO2)o1
CHEMBL64391 cxcr1_human Human Yes 4.7 IC50 = 20800 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with Tween-80-treated compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with Tween-80-treated compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
704 11 0 12 5.6 CCC(C)n1ncn(-c2ccc(N3CCN(c4ccc(OCC5COC(Cn6cncn6)(c6ccc(Cl)cc6Cl)O5)cc4)CC3)cc2)c1=O
CHEMBL365008 cxcr1_human Human No 5.7 IC50 = 2100 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
411 7 0 5 4.7 CN1CCN(CCCOc2ccc(-c3cc(-c4ccc(Cl)cc4)no3)cc2)CC1
CHEMBL25573 cxcr1_human Human No 4.7 IC50 = 21000 nM Bind
Inhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligandInhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligand
253 2 3 3 2.9 N#Cc1ccc(NC(=O)Nc2ccccc2)c(O)c1
CHEMBL218486 cxcr1_human Human No 6.7 IC50 = 215 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 expressed in CHO cells
626 8 4 7 5.1 CCC(CC)(NS(=O)(=O)c1c(Cl)ccc(N/C(=N/C#N)Nc2ccccc2Br)c1O)N1C[C@H](C)O[C@H](C)C1
CHEMBL4752486 cxcr1_human Human No 4.7 IC50 = 21700 nM Funct
Antagonist activity in CXCR1 (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 CXCR1 (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(c3ccccc3Cl)N2)c1O
CHEMBL239767 cxcr1_human Human Yes 7.7 IC50 = 22 nM Bind
Antagonist activity at CXCR1 assessed as inhibition of CXCL8 binding by cell based assayAntagonist activity at CXCR1 assessed as inhibition of CXCL8 binding by cell based assay
351 3 3 4 3.7 O=C(Nc1ccccc1Br)Nc1ccc(cc1O)[N+](=O)[O-]
CHEMBL387136 cxcr1_human Human No 7.7 IC50 = 22 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 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
CHEMBL184637 cxcr1_human Human No 7.7 IC50 = 22 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
322 2 4 3 3.5 O=C(Nc1ccc(O)cc1O)Nc1ccccc1Br
CHEMBL2324200 cxcr1_human Human No 5.7 IC50 = 2200 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
822 2 2 4 6.0 O=C1OC(c2cc(I)c(O)c(I)c2)(c2c(I)cc(O)cc2I)c2ccccc21
CHEMBL253705 cxcr1_human Human No 6.7 IC50 = 221 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
465 8 3 8 4.3 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(-c2ccsc2)co1
CHEMBL401894 cxcr1_human Human No 6.7 IC50 = 224 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
398 7 3 8 2.3 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(C)on1
CHEMBL3704558 cxcr1_human Human No 5.7 IC50 = 2245 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
CHEMBL183561 cxcr1_human Human No 4.6 IC50 = 22700 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
469 9 0 6 5.8 CN1CCN(CCCOc2ccc(-c3cc(-c4ccc(Oc5ccccc5)cc4)no3)cc2)CC1
CHEMBL4473520 cxcr1_human Human No 6.6 IC50 = 230 nM Bind
Displacement of [125I]IL-8 from CXCR1 in human neutrophils incubated for 3 hrs by gamma counting methodDisplacement of [125I]IL-8 from CXCR1 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
CHEMBL4757674 cxcr1_human Human No 4.6 IC50 = 23400 nM Funct
Antagonist activity in CXCR1 (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 CXCR1 (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
CHEMBL415446 cxcr1_human Human No 6.6 IC50 = 235 nM Bind
Displacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cells
413 7 3 7 3.4 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(C)s1
CHEMBL234186 cxcr1_human Human No 4.6 IC50 = 24000 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR1 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR1 receptor expressed in CHO cells
357 1 3 5 3.3 O=S1(=O)N=C(Nc2ccccc2Cl)Nc2c(O)cc(Cl)cc21
CHEMBL3701187 cxcr1_human Human No 5.6 IC50 = 2412 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
CHEMBL3979652 cxcr1_human Human No 6.6 IC50 = 244 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).
453 7 3 8 3.1 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)CCCO2)o1
CHEMBL404490 cxcr1_human Human No 6.6 IC50 = 244 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
417 7 3 7 3.2 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(Cl)o1
CHEMBL3609009 cxcr1_human Human No 5.6 IC50 = 2500 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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
CHEMBL365671 cxcr1_human Human No 5.6 IC50 = 2500 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
412 7 0 6 4.1 CN1CCN(CCCOc2ccc(-c3nc(-c4ccc(Cl)cc4)no3)cc2)CC1
CHEMBL254370 cxcr1_human Human No 6.6 IC50 = 254 nM Bind
Displacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR1 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
CHEMBL218115 cxcr1_human Human No 7.6 IC50 = 26 nM Bind
Displacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR1 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
CHEMBL28009 cxcr1_human Human Yes 5.6 IC50 = 2600 nM Bind
Displacement of [125I]IL-8 from CXCR1 (unknown origin) stably expressed in CHO cellsDisplacement of [125I]IL-8 from CXCR1 (unknown origin) stably expressed in CHO cells
409 2 3 3 4.4 N#Cc1ccc(NC(=O)Nc2ccccc2Br)c(O)c1Br
CHEMBL28009 cxcr1_human Human Yes 5.6 IC50 = 2600 nM Bind
Inhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligandInhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligand
409 2 3 3 4.4 N#Cc1ccc(NC(=O)Nc2ccccc2Br)c(O)c1Br
CHEMBL3701185 cxcr1_human Human No 5.6 IC50 = 2620 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
CHEMBL183061 cxcr1_human Human No 5.6 IC50 = 2700 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
328 5 0 4 4.6 CN(C)COc1ccc(-c2cc(-c3ccc(Cl)cc3)on2)cc1
CHEMBL253051 cxcr1_human Human No 6.6 IC50 = 275 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
417 7 3 7 3.2 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(Cl)o1
CHEMBL3701186 cxcr1_human Human No 5.6 IC50 = 2841 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
CHEMBL253506 cxcr1_human Human No 5.5 IC50 = 2856 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
394 7 3 7 2.4 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccncc1
CHEMBL252896 cxcr1_human Human No 6.5 IC50 = 289 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
399 7 3 9 1.7 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1nc(C)no1
CHEMBL4466314 cxcr1_human Human No 5.5 IC50 = 2900 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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
395 5 3 6 2.6 O=C(c1cccc(Nc2c(NC3C[C@@H]4CC[C@H]3C4)c(=O)c2=O)c1O)N1CCCC1
CHEMBL376621 cxcr1_human Human No 6.5 IC50 = 293 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 expressed in CHO cells
499 7 3 6 4.2 CN(C)S(=O)(=O)c1c(Cl)ccc(N/C(=N/C#N)Nc2ccccc2OCc2ccccc2)c1O
CHEMBL3609016 cxcr1_human Human No 8.5 IC50 = 3.3 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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
CHEMBL216981 cxcr1_human Human Yes 8.4 IC50 = 3.9 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
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
CHEMBL3952996 cxcr1_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).
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
CHEMBL185610 cxcr1_human Human No 5.5 IC50 = 3000 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
377 7 0 5 4.0 CN1CCN(CCCOc2ccc(-c3cc(-c4ccccc4)no3)cc2)CC1
CHEMBL1188250 cxcr1_human Human No 4.5 IC50 = 30000 nM Bind
Concentration required to inhibit [125I]-IL-8 binding towards C-X-C chemokine receptor type 1 of human expressed in CHO cellsConcentration required to inhibit [125I]-IL-8 binding towards C-X-C chemokine receptor type 1 of human expressed in CHO cells
369 3 4 3 3.9 NCc1c(Cl)ccc(NC(=O)Nc2ccccc2Br)c1O
CHEMBL535818 cxcr1_human Human No 4.5 IC50 = 30000 nM Bind
Concentration required to inhibit [125I]-IL-8 binding towards C-X-C chemokine receptor type 1 of human expressed in CHO cellsConcentration required to inhibit [125I]-IL-8 binding towards C-X-C chemokine receptor type 1 of human expressed in CHO cells
369 3 4 3 3.9 NCc1c(Cl)ccc(NC(=O)Nc2ccccc2Br)c1O
CHEMBL252698 cxcr1_human Human No 6.5 IC50 = 302 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
384 7 3 8 2.0 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccno1
CHEMBL3704562 cxcr1_human Human No 5.5 IC50 = 3031 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
CHEMBL1162935 cxcr1_human Human No 5.5 IC50 = 3058 nM Bind
Displacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR1 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
CHEMBL3426944 cxcr1_human Human Yes 7.5 IC50 = 31 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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
CHEMBL3426944 cxcr1_human Human Yes 7.5 IC50 = 31 nM Bind
Inhibition of CXCR1 (unknown origin) transfected with RBL cellsInhibition of CXCR1 (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
CHEMBL182361 cxcr1_human Human No 5.5 IC50 = 3100 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
312 5 0 4 4.0 CN(C)COc1ccc(-c2cc(-c3ccc(F)cc3)on2)cc1
CHEMBL3704570 cxcr1_human Human No 6.5 IC50 = 312 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 Cc1ccc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL3701192 cxcr1_human Human No 5.5 IC50 = 3171 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 3 9 2.3 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N4CCOCC4)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL443583 cxcr1_human Human No 5.5 IC50 = 3200 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR1 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR1 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
CHEMBL3704565 cxcr1_human Human No 6.5 IC50 = 322 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
CHEMBL3609013 cxcr1_human Human No 6.5 IC50 = 326 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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
CHEMBL283736 cxcr1_human Human No 4.5 IC50 = 33200 nM Bind
Inhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligandInhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligand
273 3 3 4 2.9 O=C(Nc1ccccc1)Nc1cccc([N+](=O)[O-])c1O
CHEMBL3938406 cxcr1_human Human No 5.5 IC50 = 3350 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
CHEMBL254516 cxcr1_human Human No 5.5 IC50 = 3376 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
493 8 3 7 4.9 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(-c2cccc(Cl)c2)o1
CHEMBL3915853 cxcr1_human Human No 5.5 IC50 = 3391 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
CHEMBL384889 cxcr1_human Human No 7.5 IC50 = 34 nM Bind
Displacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cells
411 7 3 7 3.1 Cc1ccc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C(C)C)o1
CHEMBL251890 cxcr1_human Human No 5.5 IC50 = 3434 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
527 8 3 7 5.3 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(-c2cccc(C(F)(F)F)c2)o1
CHEMBL253706 cxcr1_human Human No 6.5 IC50 = 345 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
478 8 3 9 3.9 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(-c2c(C)noc2C)co1
CHEMBL3704559 cxcr1_human Human No 5.5 IC50 = 3533 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 2.3 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N4CCC(O)C4)c3)c(=O)c2=O)C2(C)COC2)o1
CHEMBL216981 cxcr1_human Human Yes 7.4 IC50 = 36 nM Bind
Displacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR1 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
CHEMBL3909470 cxcr1_human Human No 7.4 IC50 = 36 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
CHEMBL365008 cxcr1_human Human No 5.4 IC50 = 3600 nM Funct
Inhibition of interleukin-8 induced elastase release from human neutrophilsInhibition of interleukin-8 induced elastase release from human neutrophils
411 7 0 5 4.7 CN1CCN(CCCOc2ccc(-c3cc(-c4ccc(Cl)cc4)no3)cc2)CC1
CHEMBL220860 cxcr1_human Human No 6.4 IC50 = 378 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 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
CHEMBL4067429 cxcr1_human Human Yes 5.4 IC50 = 3800 nM Bind
Antagonist activity at CXCR1 (unknown origin)Antagonist activity at CXCR1 (unknown origin)
414 4 3 5 3.2 CC1=CCC[C@H]1NC(=O)Nc1ccc(Cl)c(S(=O)(=O)[C@@]2(C)CCOC2)c1O
CHEMBL183425 cxcr1_human Human No 5.4 IC50 = 3800 nM Funct
Inhibition of interleukin-8 induced elastase release from human neutrophilsInhibition of interleukin-8 induced elastase release from human neutrophils
395 7 0 5 4.2 CN1CCN(CCCOc2ccc(-c3cc(-c4ccc(F)cc4)no3)cc2)CC1
CHEMBL3963336 cxcr1_human Human No 5.4 IC50 = 3808 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
CHEMBL4757462 cxcr1_human Human No 4.4 IC50 = 38100 nM Funct
Antagonist activity in CXCR1 (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 CXCR1 (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(c3ccc(Cl)cc3)N2)c1O
CHEMBL3986396 cxcr1_human Human No 6.4 IC50 = 384 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).
401 6 3 8 2.3 Cc1ccc(C(Nc2c(NC3=CC=CN(C)C3O)c(=O)c2=O)C2CCCS2)o1
CHEMBL3640034 cxcr1_human Human No 5.4 IC50 = 3899 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).
445 7 3 9 2.6 Cc1ccc([C@H](Nc2c(Nc3csc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL361312 cxcr1_human Human No 5.4 IC50 = 3900 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
356 7 0 4 5.0 CN(C)CCCOc1ccc(-c2cc(-c3ccc(Cl)cc3)no2)cc1
CHEMBL510437 cxcr1_human Human No 5.4 IC50 = 3910 nM Bind
Displacement of [125I]CXCL8 from CXCR1 receptor in human PMN assessed as myeloperoxidase releaseDisplacement of [125I]CXCL8 from CXCR1 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
CHEMBL182361 cxcr1_human Human No 5.4 IC50 = 4000 nM Funct
Inhibition of interleukin-8 induced elastase release from human neutrophilsInhibition of interleukin-8 induced elastase release from human neutrophils
312 5 0 4 4.0 CN(C)COc1ccc(-c2cc(-c3ccc(F)cc3)on2)cc1
CHEMBL3609003 cxcr1_human Human No 5.4 IC50 = 4100 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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
CHEMBL222075 cxcr1_human Human No 6.4 IC50 = 411 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 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
CHEMBL251811 cxcr1_human Human No 6.4 IC50 = 412 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
433 7 3 7 3.7 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc2ccccc2o1
CHEMBL4746803 cxcr1_human Human No 4.4 IC50 = 41800 nM Funct
Antagonist activity in CXCR1 (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 CXCR1 (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
CHEMBL3904195 cxcr1_human Human No 7.4 IC50 = 42 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
CHEMBL27446 cxcr1_human Human Yes 5.4 IC50 = 4200 nM Bind
Inhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligandInhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligand
365 2 3 3 4.3 N#Cc1ccc(NC(=O)Nc2ccccc2Br)c(O)c1Cl
CHEMBL3901913 cxcr1_human Human No 7.4 IC50 = 43 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
CHEMBL3609004 cxcr1_human Human No 5.4 IC50 = 4300 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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
CHEMBL183222 cxcr1_human Human No 5.4 IC50 = 4317 nM Bind
Concentration required to inhibit [125I]-IL-8 binding towards C-X-C chemokine receptor type 1 of human expressed in CHO cellsConcentration required to inhibit [125I]-IL-8 binding towards C-X-C chemokine receptor type 1 of human expressed in CHO cells
447 4 3 4 3.7 CN(C)S(=O)(=O)c1c(Cl)ccc(NC(=O)Nc2ccccc2Br)c1O
CHEMBL3951994 cxcr1_human Human No 7.4 IC50 = 44 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
CHEMBL413959 cxcr1_human Human No 5.4 IC50 = 4400 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
328 5 0 4 4.6 CN(C)COc1ccccc1-c1cc(-c2ccc(Cl)cc2)on1
CHEMBL3609021 cxcr1_human Human No 6.4 IC50 = 444 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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
447 8 3 8 1.7 O=C(Nc1ccc(F)cc1)c1cnc(N(Cc2ccc(B(O)O)cn2)Cc2ccco2)nc1
CHEMBL496452 cxcr1_human Human No 5.4 IC50 = 4500 nM Bind
Displacement of [125I]IL8 from human recombinant IL8 type A receptorDisplacement of [125I]IL8 from human recombinant IL8 type A receptor
474 6 2 5 5.2 CC(=O)O[C@H]1C=C2[C@@H]3CC[C@H]([C@H](C)CCCC(C)C)[C@@]3(C)C[C@H]3O[C@@]23[C@@]2(C)CC[C@H](O)C[C@]12O
CHEMBL1520590 cxcr1_human Human Yes 5.4 IC50 = 4500 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
302 1 5 7 2.0 O=c1c(O)c(-c2ccc(O)c(O)c2)oc2cc(O)cc(O)c12
CHEMBL50 cxcr1_human Human Yes 5.4 IC50 = 4500 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
302 1 5 7 2.0 O=c1c(O)c(-c2ccc(O)c(O)c2)oc2cc(O)cc(O)c12
CHEMBL365671 cxcr1_human Human No 5.4 IC50 = 4500 nM Funct
Inhibition of interleukin-8 induced elastase release from human neutrophilsInhibition of interleukin-8 induced elastase release from human neutrophils
412 7 0 6 4.1 CN1CCN(CCCOc2ccc(-c3nc(-c4ccc(Cl)cc4)no3)cc2)CC1
CHEMBL3951994 cxcr1_human Human No 5.3 IC50 = 4554 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
CHEMBL24912 cxcr1_human Human Yes 4.3 IC50 = 46200 nM Bind
Inhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligandInhibition of binding of IL-8 to membranes of cloned CXC chemokine receptor 1 expressed in CHO Cells using [125I]IL-8 radioligand
273 3 3 4 2.9 O=C(Nc1ccccc1)Nc1cc([N+](=O)[O-])ccc1O
CHEMBL253050 cxcr1_human Human No 6.3 IC50 = 463 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
461 7 3 7 3.4 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(Br)o1
CHEMBL4786074 cxcr1_human Human No 5.3 IC50 = 4700 nM Funct
Antagonist activity in CXCR1 (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 CXCR1 (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
407 4 3 6 2.9 CC(C)S(=O)(=O)c1c(Cl)ccc(NC2=NC(=O)C(c3ccccc3)N2)c1O
CHEMBL4799848 cxcr1_human Human No 4.3 IC50 = 47800 nM Funct
Antagonist activity in CXCR1 (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 CXCR1 (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
CHEMBL3934321 cxcr1_human Human No 6.3 IC50 = 483 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
CHEMBL402952 cxcr1_human Human No 5.3 IC50 = 4870 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
493 8 3 7 4.9 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(-c2ccccc2Cl)o1
CHEMBL3701193 cxcr1_human Human No 5.3 IC50 = 4957 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
CHEMBL64391 cxcr1_human Human Yes 5.3 IC50 = 5000 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with centrifuged compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with centrifuged compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
704 11 0 12 5.6 CCC(C)n1ncn(-c2ccc(N3CCN(c4ccc(OCC5COC(Cn6cncn6)(c6ccc(Cl)cc6Cl)O5)cc4)CC3)cc2)c1=O
CHEMBL1520590 cxcr1_human Human Yes 5.3 IC50 = 5011.9 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
302 1 5 7 2.0 O=c1c(O)c(-c2ccc(O)c(O)c2)oc2cc(O)cc(O)c12
CHEMBL50 cxcr1_human Human Yes 5.3 IC50 = 5011.9 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
302 1 5 7 2.0 O=c1c(O)c(-c2ccc(O)c(O)c2)oc2cc(O)cc(O)c12
CHEMBL64391 cxcr1_human Human Yes 5.3 IC50 = 5011.9 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with centrifuged compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with centrifuged compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
704 11 0 12 5.6 CCC(C)n1ncn(-c2ccc(N3CCN(c4ccc(OCC5COC(Cn6cncn6)(c6ccc(Cl)cc6Cl)O5)cc4)CC3)cc2)c1=O
CHEMBL3902863 cxcr1_human Human No 6.3 IC50 = 508 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
CHEMBL386505 cxcr1_human Human No 6.3 IC50 = 512 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 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
CHEMBL3704567 cxcr1_human Human No 5.3 IC50 = 5225 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).
403 6 3 8 2.9 Cc1ccc(C(Nc2c(Nc3ccc(Cl)nc3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL401938 cxcr1_human Human No 6.3 IC50 = 526 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
460 8 3 8 3.7 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(-c2ccncc2)co1
CHEMBL4763312 cxcr1_human Human No 5.3 IC50 = 5400 nM Funct
Antagonist activity in CXCR1 (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 CXCR1 (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
423 6 3 7 2.1 COCCS(=O)(=O)c1c(Cl)ccc(NC2=NC(=O)C(c3ccccc3)N2)c1O
CHEMBL184319 cxcr1_human Human No 5.3 IC50 = 5400 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
334 5 0 4 4.8 c1ccc(-c2cc(-c3ccc(OCN4CCCCC4)cc3)no2)cc1
CHEMBL3943808 cxcr1_human Human No 5.3 IC50 = 5440 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
CHEMBL4747035 cxcr1_human Human No 4.3 IC50 = 54600 nM Funct
Antagonist activity in CXCR1 (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 CXCR1 (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 6 3 6 2.7 CCCCC1NC(Nc2ccc(Cl)c(S(=O)(=O)C(C)C)c2O)=NC1=O
CHEMBL218387 cxcr1_human Human No 7.3 IC50 = 55 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 expressed in CHO cells
471 4 3 5 3.4 CN(C)S(=O)(=O)c1c(Cl)ccc(N/C(=N/C#N)Nc2ccccc2Br)c1O
CHEMBL216603 cxcr1_human Human No 7.3 IC50 = 55 nM Bind
Displacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR1 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
CHEMBL401939 cxcr1_human Human No 7.3 IC50 = 55 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
461 7 3 7 3.4 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(Br)co1
CHEMBL451438 cxcr1_human Human No 5.3 IC50 = 5500 nM Bind
Displacement of [125I]IL8 from human recombinant IL8 type A receptorDisplacement of [125I]IL8 from human recombinant IL8 type A receptor
576 8 2 8 5.3 CC(=O)O[C@H]1CC[C@]2(C)C3=C([C@H](OC(C)=O)[C@H](OC(C)=O)[C@@]2(O)C1)[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)C[C@H]3O
CHEMBL3891755 cxcr1_human Human No 6.3 IC50 = 552 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
CHEMBL3704556 cxcr1_human Human No 5.3 IC50 = 5541 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 8 3 8 2.6 COc1cccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)COC2)c1
CHEMBL3704569 cxcr1_human Human No 6.3 IC50 = 566 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
CHEMBL253052 cxcr1_human Human No 6.3 IC50 = 568 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
433 8 3 7 3.5 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(C(F)F)o1
CHEMBL3935902 cxcr1_human Human No 6.2 IC50 = 580 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
CHEMBL218744 cxcr1_human Human No 6.2 IC50 = 582 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 expressed in CHO cells
564 8 4 7 3.6 CCC(CC)(NS(=O)(=O)c1cccc(N/C(=N/C#N)Nc2ccccc2Br)c1O)N1CCOCC1
CHEMBL363746 cxcr1_human Human No 5.2 IC50 = 6000 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
445 7 0 5 5.0 CN1CCN(CCCOc2ccc(-c3cc(-c4cccc(C(F)(F)F)c4)no3)cc2)CC1
CHEMBL184185 cxcr1_human Human No 5.2 IC50 = 6037 nM Bind
Concentration required to inhibit [125I]-IL-8 binding towards C-X-C chemokine receptor type 1 of human expressed in CHO cellsConcentration required to inhibit [125I]-IL-8 binding towards C-X-C chemokine receptor type 1 of human expressed in CHO cells
383 3 4 3 3.6 NC(=O)c1c(Cl)ccc(NC(=O)Nc2ccccc2Br)c1O
CHEMBL3701188 cxcr1_human Human No 6.2 IC50 = 604 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
CHEMBL404250 cxcr1_human Human No 5.2 IC50 = 6062 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
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
CHEMBL3609002 cxcr1_human Human No 6.2 IC50 = 611 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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(NCc2cccc(B(O)O)c2)nc1
CHEMBL253714 cxcr1_human Human No 7.2 IC50 = 62 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
417 7 3 7 3.2 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(Cl)co1
CHEMBL185268 cxcr1_human Human No 5.2 IC50 = 6200 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
349 5 0 5 3.6 CN1CCN(COc2ccc(-c3cc(-c4ccccc4)on3)cc2)CC1
CHEMBL221039 cxcr1_human Human No 5.2 IC50 = 6204 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 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
CHEMBL3704571 cxcr1_human Human No 6.2 IC50 = 650 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 CCN(C)C(=O)c1cccc(Nc2c(N[C@@H](c3ccc(C)o3)C3(C)COC3)c(=O)c2=O)c1O
CHEMBL3701189 cxcr1_human Human No 5.2 IC50 = 6510 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).
412 7 4 8 2.9 Cc1ccc(C(Nc2c(Nc3cccc(C(C)O)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL3947915 cxcr1_human Human No 6.2 IC50 = 652 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
CHEMBL3951994 cxcr1_human Human No 6.2 IC50 = 661 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
CHEMBL3701194 cxcr1_human Human No 5.2 IC50 = 6621 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
CHEMBL3640000 cxcr1_human Human No 6.2 IC50 = 666 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
CHEMBL252851 cxcr1_human Human No 7.2 IC50 = 67 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
383 7 3 7 2.6 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccco1
CHEMBL183819 cxcr1_human Human Yes 5.2 IC50 = 6700 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
322 7 0 4 4.3 CN(C)CCCOc1ccc(-c2cc(-c3ccccc3)no2)cc1
CHEMBL3609011 cxcr1_human Human No 6.2 IC50 = 681 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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
CHEMBL3951994 cxcr1_human Human No 6.2 IC50 = 692 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
CHEMBL3609018 cxcr1_human Human No 8.2 IC50 = 7 nM Funct
Antagonist activity at CXCR1 (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 CXCR1 (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
CHEMBL246108 cxcr1_human Human Yes 8.1 IC50 = 7.3 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 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
CHEMBL401893 cxcr1_human Human No 6.2 IC50 = 703 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
400 7 3 8 2.5 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1nccs1
CHEMBL3906175 cxcr1_human Human No 6.2 IC50 = 711 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
CHEMBL218334 cxcr1_human Human No 5.1 IC50 = 7289 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 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
CHEMBL3704574 cxcr1_human Human No 5.1 IC50 = 7386 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 Cc1ccc([C@@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)COC2)o1
CHEMBL425985 cxcr1_human Human No 6.1 IC50 = 752 nM Bind
Displacement of [125I]IL8 from CXCR1 expressed in CHO cellsDisplacement of [125I]IL8 from CXCR1 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
CHEMBL399203 cxcr1_human Human No 5.1 IC50 = 7600 nM Bind
Displacement of human recombinant [125I]IL8 from CXCR1 receptor expressed in CHO cellsDisplacement of human recombinant [125I]IL8 from CXCR1 receptor expressed in CHO cells
426 4 3 8 3.7 O=[N+]([O-])c1cc(O)c2c(c1)S(=O)(=O)N=C(Nc1ccccc1Oc1ccccc1)N2
CHEMBL185176 cxcr1_human Human No 5.1 IC50 = 7600 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
348 5 0 4 4.7 CN1CCC(COc2ccc(-c3cc(-c4ccccc4)on3)cc2)CC1
CHEMBL3704564 cxcr1_human Human No 5.1 IC50 = 7685 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
CHEMBL3951994 cxcr1_human Human No 7.1 IC50 = 77 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
CHEMBL216602 cxcr1_human Human No 6.1 IC50 = 775 nM Bind
Displacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cells
383 6 3 7 2.5 Cc1ccc([C@@H](C)Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)o1
CHEMBL104 cxcr1_human Human Yes 5.1 IC50 = 7900 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with Tween-80-treated compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with Tween-80-treated compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
344 4 0 2 5.4 Clc1ccccc1C(c1ccccc1)(c1ccccc1)n1ccnc1
CHEMBL104 cxcr1_human Human Yes 5.1 IC50 = 7943.3 nM Bind
Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with Tween-80-treated compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assayInhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins with Tween-80-treated compound solution measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay
344 4 0 2 5.4 Clc1ccccc1C(c1ccccc1)(c1ccccc1)n1ccnc1
CHEMBL430116 cxcr1_human Human No 6.1 IC50 = 795 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
384 7 3 8 2.0 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ncco1
CHEMBL252697 cxcr1_human Human No 6.1 IC50 = 805 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
384 7 3 8 2.0 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cocn1
CHEMBL385715 cxcr1_human Human No 7.1 IC50 = 81 nM Bind
Displacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cells
399 7 3 7 3.1 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cccs1
CHEMBL184583 cxcr1_human Human No 5.1 IC50 = 8100 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
328 5 0 4 4.6 CN(C)COc1cccc(-c2cc(-c3ccc(Cl)cc3)on2)c1
CHEMBL3900726 cxcr1_human Human No 6.1 IC50 = 812 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
CHEMBL252897 cxcr1_human Human No 6.1 IC50 = 812 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
383 7 3 7 2.6 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccoc1
CHEMBL3979652 cxcr1_human Human No 6.1 IC50 = 819 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).
453 7 3 8 3.1 Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)CCCO2)o1
CHEMBL3704564 cxcr1_human Human No 6.1 IC50 = 827 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
CHEMBL3909470 cxcr1_human Human No 7.1 IC50 = 85 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
CHEMBL252852 cxcr1_human Human No 6.1 IC50 = 854 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
411 8 3 7 3.2 CCc1ccc(C(CC)Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)o1
CHEMBL3901913 cxcr1_human Human No 6.1 IC50 = 859 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
CHEMBL3342269 cxcr1_human Human Yes 6.1 IC50 = 880 nM Funct
Antagonist activity at human CXCR1 expressed in HEK293 cells assessed as inhibition of CXCL8-induced intracellular Ca2+ release by fluorescence based calcium flux assayAntagonist activity at human CXCR1 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
CHEMBL3935902 cxcr1_human Human No 7.1 IC50 = 89 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
CHEMBL185476 cxcr1_human Human No 5.1 IC50 = 8900 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
397 6 0 5 4.3 CN1CCN(CCOc2ccc(-c3cc(-c4ccc(Cl)cc4)on3)cc2)CC1
CHEMBL3968340 cxcr1_human Human No 5.1 IC50 = 8907 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(N[C@H](c3ccc(C)o3)[C@@H]3CCCS3)c(=O)c2=O)c1F
CHEMBL3704572 cxcr1_human Human No 6.1 IC50 = 897 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 cxcr1_human Human Yes 6.0 IC50 = 903 nM Bind
Inhibition of CXCR1 (unknown origin) transfected with RBL cellsInhibition of CXCR1 (unknown origin) transfected with RBL cells
382 6 3 5 2.4 Fc1ccc(cc1)NC(=O)c1ccc(nc1)SCc1ccccc1B(O)O
CHEMBL218964 cxcr1_human Human No 6.0 IC50 = 910 nM Bind
Displacement of [125I]hCXCL8 from human CXCR1 receptor expressed in BaF3 cellsDisplacement of [125I]hCXCL8 from human CXCR1 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
CHEMBL4742368 cxcr1_human Human No 5.0 IC50 = 9100 nM Funct
Antagonist activity in CXCR1 (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 CXCR1 (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
CHEMBL401939 cxcr1_human Human No 6.0 IC50 = 917 nM Bind
Inhibition of CXCR1-mediated chemotaxis in Ba/F3 cells expressing human CXCR1Inhibition of CXCR1-mediated chemotaxis in Ba/F3 cells expressing human CXCR1
461 7 3 7 3.4 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(Br)co1
CHEMBL253498 cxcr1_human Human No 7.0 IC50 = 93 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
461 7 3 7 3.4 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(Br)co1
CHEMBL364397 cxcr1_human Human No 5.0 IC50 = 9600 nM Bind
Inhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligandInhibitory concentration against interleukin-8 receptor of human neutrophils by using [125I]IL-8 (0.125 nM) as radioligand
411 7 0 5 4.7 CN1CCN(CCCOc2ccc(-c3cc(-c4cccc(Cl)c4)no3)cc2)CC1
CHEMBL404249 cxcr1_human Human Yes 7.0 IC50 = 99 nM Bind
Inhibition of CXCR1Inhibition of CXCR1
397 7 3 7 2.9 CCC(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(C)o1
CHEMBL3701190 cxcr1_human Human No 5.0 IC50 = 9999 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
CHEMBL3704557 cxcr1_human Human No 5.0 IC50 = 9999 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 8 3 8 2.6 COc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)COC2)cc1
CHEMBL3704560 cxcr1_human Human No 5.0 IC50 = 9999 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)C1CCCN1C(=O)c1cccc(Nc2c(NC(c3ccc(C)o3)C3(C)COC3)c(=O)c2=O)c1O
CHEMBL3704566 cxcr1_human Human No 5.0 IC50 = 9999 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
CHEMBL3704568 cxcr1_human Human No 5.0 IC50 = 9999 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
CHEMBL523645 cxcr1_human Human No 8.0 Ki = 10 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
487 7 3 7 3.7 Cc1ccc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C(F)(F)C(F)(F)F)o1
CHEMBL247150 cxcr1_human Human No 8.0 Ki = 10 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
437 8 3 7 3.7 CC(C)c1coc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2CC2)c1
CHEMBL394899 cxcr1_human Human No 8.0 Ki = 10 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
439 7 3 7 3.9 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(C(C)(C)C)co1
CHEMBL473145 cxcr1_human Human No 7.0 Ki = 100 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
437 7 3 7 3.1 CN(C)C(=O)c1cccc(Nc2c(N[C@H](CC(F)(F)F)c3ccco3)c(=O)c2=O)c1O
CHEMBL253104 cxcr1_human Human No 5.0 Ki = 10000 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
429 6 3 9 2.7 CN(C)C(=O)c1cccc(Nc2n[s+]([O-])nc2NCc2ccc3c(c2)OCO3)c1O
CHEMBL523807 cxcr1_human Human No 7.0 Ki = 103 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
491 6 3 7 4.0 CN(C)C(=O)c1cccc(Nc2c(N[C@@H](c3cc(Cl)c(Cl)o3)C(F)(F)F)c(=O)c2=O)c1O
CHEMBL247149 cxcr1_human Human No 8.0 Ki = 11 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
439 8 3 7 4.0 CC(C)c1coc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C(C)C)c1
CHEMBL253702 cxcr1_human Human No 6.0 Ki = 1100 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
459 5 3 7 2.6 Cc1ccc([C@H](NC2=NS(=O)(=O)N=C2Nc2cccc(C(=O)N(C)C)c2O)C2(C)CC2)o1
CHEMBL253304 cxcr1_human Human No 5.9 Ki = 1220 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
413 7 3 7 3.9 CC[C@@H](Nc1n[s+]([O-])nc1Nc1cccc(C(=O)N(C)C)c1O)c1ccccc1
CHEMBL550880 cxcr1_human Human No 5.9 Ki = 1221 nM Bind
Displacement of human [125I]IL-8 from human CXCR1Displacement of human [125I]IL-8 from human CXCR1
433 7 3 7 3.7 CC[C@@H](Nc1c(Nc2cc(Cl)cc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cccs1
CHEMBL245500 cxcr1_human Human No 6.9 Ki = 123 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
413 7 3 7 3.4 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1sccc1C
CHEMBL561812 cxcr1_human Human No 6.9 Ki = 123 nM Bind
Displacement of human [125I]IL-8 from human CXCR1Displacement of human [125I]IL-8 from human CXCR1
421 8 3 6 3.8 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C(C)C)c2O)c(=O)c1=O)c1ccccc1
CHEMBL490688 cxcr1_human Human No 6.9 Ki = 126 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
483 6 3 9 4.7 CN(C)C(=O)c1cccc(Nc2nsnc2N[C@@H](c2ccc3c(c2)OCCO3)C(C)(C)C)c1O
CHEMBL403023 cxcr1_human Human No 6.9 Ki = 129 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
481 4 3 7 3.2 CN(C)C(=O)c1cccc(NC2=NS(=O)(=O)N=C2N[C@@H](c2ccc(Cl)o2)C(C)(C)C)c1O
CHEMBL462155 cxcr1_human Human No 7.9 Ki = 13 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
468 8 3 9 5.1 Cc1ccc([C@H](Nc2nsnc2Nc2cccc(C(=O)N(C)CCC#N)c2O)C(C)(C)C)o1
CHEMBL518201 cxcr1_human Human No 7.9 Ki = 13 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
401 7 3 8 4.2 CC[C@@H](Nc1nsnc1Nc1cccc(C(=O)N(C)C)c1O)c1ccc(C)o1
CHEMBL253305 cxcr1_human Human No 6.9 Ki = 130 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
441 6 3 7 4.6 CN(C)C(=O)c1cccc(Nc2n[s+]([O-])nc2N[C@@H](c2ccccc2)C(C)(C)C)c1O
CHEMBL455431 cxcr1_human Human No 7.9 Ki = 14 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
429 6 3 8 4.8 Cc1ccc([C@H](Nc2nsnc2Nc2cccc(C(=O)N(C)C)c2O)C(C)(C)C)o1
CHEMBL462331 cxcr1_human Human No 7.9 Ki = 14 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
454 8 3 9 4.8 CN(CCC#N)C(=O)c1cccc(Nc2nsnc2N[C@@H](c2ccco2)C(C)(C)C)c1O
CHEMBL464012 cxcr1_human Human No 7.9 Ki = 14 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
431 7 3 8 4.9 Cc1ccc([C@H](Nc2nsnc2Nc2cccc(C(=O)N(C)C)c2O)C(C)C)s1
CHEMBL246107 cxcr1_human Human No 7.9 Ki = 14 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
524 12 3 9 3.2 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(CCCCN2CCOCC2)co1
CHEMBL247356 cxcr1_human Human No 7.9 Ki = 14 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
453 7 3 7 4.3 CC(C)c1coc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C(C)(C)C)c1
CHEMBL415446 cxcr1_human Human No 6.8 Ki = 146 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
413 7 3 7 3.4 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(C)s1
CHEMBL508938 cxcr1_human Human No 7.8 Ki = 15 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
415 6 3 8 4.5 CN(C)C(=O)c1cccc(Nc2nsnc2N[C@@H](c2ccco2)C(C)(C)C)c1O
CHEMBL510437 cxcr1_human Human No 7.8 Ki = 15 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
415 7 3 8 4.4 Cc1ccc([C@H](Nc2nsnc2Nc2cccc(C(=O)N(C)C)c2O)C(C)C)o1
CHEMBL514001 cxcr1_human Human No 7.8 Ki = 16 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
415 7 3 7 2.8 Cc1ccc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)[C@H](C)F)o1
CHEMBL462024 cxcr1_human Human No 7.8 Ki = 16 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
409 7 3 7 4.3 CN(C)C(=O)c1cccc(Nc2nsnc2N[C@@H](c2ccccc2)C2CC2)c1O
CHEMBL442799 cxcr1_human Human No 7.8 Ki = 16 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
465 7 3 7 3.9 CC(C)c1coc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C(F)(F)F)c1
CHEMBL518696 cxcr1_human Human No 7.8 Ki = 18 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
471 6 3 9 4.6 Cc1ccc([C@H](Nc2nsnc2Nc2cccc(C(=O)N3CCOCC3)c2O)C(C)(C)C)o1
CHEMBL216981 cxcr1_human Human Yes 7.8 Ki = 18 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
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
CHEMBL253922 cxcr1_human Human No 6.7 Ki = 188 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
461 6 3 7 2.9 CCC(C)(C)[C@@H](NC1=NS(=O)(=O)N=C1Nc1cccc(C(=O)N(C)C)c1O)c1ccco1
CHEMBL216981 cxcr1_human Human Yes 7.7 Ki = 20 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
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
CHEMBL491135 cxcr1_human Human No 7.7 Ki = 20 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
457 6 3 7 3.4 CN(C)C(=O)c1cccc(Nc2c(N[C@@H](c3cc(Cl)co3)C(F)(F)F)c(=O)c2=O)c1O
CHEMBL461816 cxcr1_human Human No 7.7 Ki = 20 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
433 7 3 7 4.5 CC[C@@H](Nc1nsnc1Nc1cccc(C(=O)N(C)C)c1O)c1cc(F)cc(F)c1
CHEMBL404381 cxcr1_human Human No 5.7 Ki = 2000 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
515 4 3 8 2.7 CN(C)C(=O)c1cccc(NC2=NS(=O)(=O)N=C2N[C@@H](c2ccc3c(c2)OCCO3)C(C)(C)C)c1O
CHEMBL562950 cxcr1_human Human No 5.7 Ki = 2068 nM Bind
Displacement of human [125I]IL-8 from human CXCR1Displacement of human [125I]IL-8 from human CXCR1
477 7 3 7 3.8 CC[C@@H](Nc1c(Nc2cc(Br)cc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cccs1
CHEMBL403547 cxcr1_human Human No 7.7 Ki = 21 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
431 6 3 8 4.1 CN(C)C(=O)c1cccc(Nc2n[s+]([O-])nc2N[C@@H](c2ccco2)C(C)(C)C)c1O
CHEMBL464509 cxcr1_human Human No 7.7 Ki = 21 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
397 7 3 7 4.3 CC[C@@H](Nc1nsnc1Nc1cccc(C(=O)N(C)C)c1O)c1ccccc1
CHEMBL556656 cxcr1_human Human No 7.7 Ki = 21 nM Bind
Displacement of human [125I]IL-8 from human CXCR1Displacement of human [125I]IL-8 from human CXCR1
435 7 4 7 2.5 CC[C@@H](Nc1c(Nc2cccc(C(=O)N3CC[C@H](O)C3)c2O)c(=O)c1=O)c1ccccc1
CHEMBL385715 cxcr1_human Human No 6.7 Ki = 210 nM Bind
Displacement of human [125I]IL-8 from human CXCR1Displacement of human [125I]IL-8 from human CXCR1
399 7 3 7 3.1 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cccs1
CHEMBL523437 cxcr1_human Human No 7.7 Ki = 22 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
447 8 3 7 3.5 CCC(F)(F)[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(C)o1
CHEMBL253306 cxcr1_human Human No 6.6 Ki = 234 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
417 7 3 8 3.8 CC[C@@H](Nc1n[s+]([O-])nc1Nc1cccc(C(=O)N(C)C)c1O)c1ccc(C)o1
CHEMBL491487 cxcr1_human Human No 7.6 Ki = 24 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
429 7 3 7 3.2 Cc1ccc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C(C)(C)F)o1
CHEMBL393900 cxcr1_human Human No 7.6 Ki = 24 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
413 7 3 7 3.4 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(C)cs1
CHEMBL523769 cxcr1_human Human No 7.6 Ki = 25 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
461 8 3 7 4.0 CC(C)c1coc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C(C)(F)F)c1
CHEMBL550945 cxcr1_human Human No 5.6 Ki = 2797 nM Bind
Displacement of human [125I]IL-8 from human CXCR1Displacement of human [125I]IL-8 from human CXCR1
413 7 3 7 3.4 CC[C@@H](Nc1c(Nc2cc(C)cc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cccs1
CHEMBL252289 cxcr1_human Human No 5.6 Ki = 2800 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
500 5 3 8 2.1 CC[C@@H](NC1=NS(=O)(=O)N=C1Nc1cccc(C(=O)N(C)C)c1O)c1ccc2c(c1)OCCN2C
CHEMBL246733 cxcr1_human Human No 6.6 Ki = 283 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
465 8 3 7 4.6 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(C2CCCCC2)co1
CHEMBL246108 cxcr1_human Human Yes 8.5 Ki = 3 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 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
CHEMBL491506 cxcr1_human Human No 7.5 Ki = 30 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
433 7 3 7 3.1 Cc1ccoc1[C@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)C(C)(F)F
CHEMBL246318 cxcr1_human Human No 7.5 Ki = 30 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
453 10 3 7 4.5 CCC(CC)c1coc([C@@H](CC)Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)c1
CHEMBL556862 cxcr1_human Human No 7.5 Ki = 30 nM Bind
Displacement of human [125I]IL-8 from human CXCR1Displacement of human [125I]IL-8 from human CXCR1
463 8 4 7 3.0 CC[C@@H](Nc1c(Nc2cccc(C(=O)N3CCCC3C(=O)O)c2O)c(=O)c1=O)c1ccccc1
CHEMBL491134 cxcr1_human Human No 7.5 Ki = 34 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
457 6 3 7 3.4 CN(C)C(=O)c1cccc(Nc2c(N[C@@H](c3ccc(Cl)o3)C(F)(F)F)c(=O)c2=O)c1O
CHEMBL462156 cxcr1_human Human No 7.5 Ki = 34 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
496 9 3 9 5.9 CC(C)c1coc([C@H](Nc2nsnc2Nc2cccc(C(=O)N(C)CCC#N)c2O)C(C)(C)C)c1
CHEMBL246106 cxcr1_human Human No 7.5 Ki = 34 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
439 10 3 7 3.9 CCCCc1coc([C@@H](CC)Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)c1
CHEMBL455209 cxcr1_human Human No 7.5 Ki = 35 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
401 7 3 8 4.2 CC[C@@H](Nc1nsnc1Nc1cccc(C(=O)N(C)C)c1O)c1cc(C)co1
CHEMBL517430 cxcr1_human Human No 7.4 Ki = 36 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
437 6 3 7 4.4 CN(C)C(=O)c1cccc(Nc2nsnc2NC(c2ccccc2)C(F)(F)F)c1O
CHEMBL252911 cxcr1_human Human No 6.4 Ki = 375 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
429 7 3 8 3.9 CN(C)C(=O)c1cccc(Nc2n[s+]([O-])nc2N[C@@H](c2ccco2)C2(C)CC2)c1O
CHEMBL245697 cxcr1_human Human No 6.4 Ki = 379 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
411 8 3 7 3.2 CCc1ccoc1[C@@H](CC)Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O
CHEMBL403206 cxcr1_human Human No 7.4 Ki = 38 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
445 6 3 8 4.5 Cc1ccc([C@H](Nc2n[s+]([O-])nc2Nc2cccc(C(=O)N(C)C)c2O)C(C)(C)C)o1
CHEMBL518802 cxcr1_human Human No 7.4 Ki = 38 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
497 6 3 8 5.8 Cc1ccc([C@H](Nc2nsnc2Nc2ccc(C(F)(F)F)c(C(=O)N(C)C)c2O)C(C)(C)C)o1
CHEMBL562781 cxcr1_human Human No 6.4 Ki = 381 nM Bind
Displacement of human [125I]IL-8 from human CXCR1Displacement of human [125I]IL-8 from human CXCR1
407 7 3 6 3.3 CC[C@@H](Nc1c(Nc2c(C)ccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccccc1
CHEMBL254370 cxcr1_human Human No 7.4 Ki = 40 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
393 7 3 6 3.0 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccccc1
CHEMBL464301 cxcr1_human Human No 7.4 Ki = 40 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
433 6 3 6 3.1 CN(C)C(=O)c1cccc(Nc2c(N[C@@H](c3ccccc3)C(F)(F)F)c(=O)c2=O)c1O
CHEMBL254370 cxcr1_human Human No 7.4 Ki = 40 nM Bind
Displacement of human [125I]IL-8 from human CXCR1Displacement of human [125I]IL-8 from human CXCR1
393 7 3 6 3.0 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccccc1
CHEMBL402144 cxcr1_human Human No 5.4 Ki = 4010 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
445 7 3 7 4.3 CC(C)[C@@H](Nc1n[s+]([O-])nc1Nc1cccc(C(=O)N(C)C)c1O)c1cccc(F)c1
CHEMBL562286 cxcr1_human Human No 7.4 Ki = 41 nM Bind
Displacement of human [125I]IL-8 from human CXCR1Displacement of human [125I]IL-8 from human CXCR1
448 7 3 7 2.7 CC[C@@H](Nc1c(Nc2cccc(C(=O)N3CCN(C)CC3)c2O)c(=O)c1=O)c1ccccc1
CHEMBL570042 cxcr1_human Human No 5.4 Ki = 4100 nM Bind
Displacement of [125I]IL-8 from human CXCR1 expressed in mouse BaF3 cells by liquid scintillation countingDisplacement of [125I]IL-8 from human CXCR1 expressed in mouse BaF3 cells by liquid scintillation counting
394 7 3 7 2.3 CCN(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccccc1
CHEMBL472749 cxcr1_human Human No 7.4 Ki = 43 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
401 7 3 7 2.5 C[C@H](F)[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccco1
CHEMBL464302 cxcr1_human Human No 7.4 Ki = 43 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
363 5 3 7 3.5 C[C@H](Nc1nsnc1Nc1cccc(C(=O)N(C)C)c1O)C(C)(C)C
CHEMBL518355 cxcr1_human Human No 7.4 Ki = 44 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
465 6 3 7 5.4 CN(C)C(=O)c1cccc(Nc2nsnc2N[C@@H](c2ccc3c(c2)CCC3)C(C)(C)C)c1O
CHEMBL253495 cxcr1_human Human No 7.3 Ki = 46 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
501 4 3 8 2.7 CN(C)C(=O)c1cccc(NC2=NS(=O)(=O)N=C2N[C@@H](c2ccc3c(c2)OCO3)C(C)(C)C)c1O
CHEMBL403936 cxcr1_human Human No 6.3 Ki = 484 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
379 5 3 7 3.2 C[C@H](Nc1n[s+]([O-])nc1Nc1cccc(C(=O)N(C)C)c1O)C(C)(C)C
CHEMBL516184 cxcr1_human Human No 8.3 Ki = 5 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
415 7 3 7 2.8 Cc1coc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)[C@H](C)F)c1
CHEMBL254943 cxcr1_human Human No 7.3 Ki = 50 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
445 7 3 8 4.4 Cc1cc([C@H](Nc2n[s+]([O-])nc2Nc2cccc(C(=O)N(C)C)c2O)C(C)C)oc1C
CHEMBL246941 cxcr1_human Human No 7.3 Ki = 50 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
411 7 3 7 3.3 CC(C)c1coc([C@@H](C)Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)c1
CHEMBL522959 cxcr1_human Human No 7.3 Ki = 52 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
469 6 3 9 4.6 CN(C)C(=O)c1cccc(Nc2nsnc2N[C@@H](c2ccc3c(c2)OCO3)C(C)(C)C)c1O
CHEMBL585928 cxcr1_human Human No 5.3 Ki = 5200 nM Bind
Displacement of [125I]IL-8 from human CXCR1 expressed in mouse BaF3 cells by liquid scintillation countingDisplacement of [125I]IL-8 from human CXCR1 expressed in mouse BaF3 cells by liquid scintillation counting
395 7 3 8 1.7 CCN(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccccn1
CHEMBL455430 cxcr1_human Human No 7.3 Ki = 53 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
441 6 3 8 4.3 Cc1ccc([C@H](Nc2nsnc2Nc2cccc(C(=O)N(C)C)c2O)C(F)(F)F)o1
CHEMBL246731 cxcr1_human Human No 7.3 Ki = 53 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
451 8 3 7 4.2 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(C2CCCC2)co1
CHEMBL563875 cxcr1_human Human No 7.3 Ki = 54 nM Bind
Displacement of human [125I]IL-8 from human CXCR1Displacement of human [125I]IL-8 from human CXCR1
424 7 3 8 2.9 CC[C@@H](Nc1c(Nc2cc(C#N)cc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cccs1
CHEMBL253496 cxcr1_human Human No 5.2 Ki = 5950 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
433 5 3 7 2.2 CC[C@@H](NC1=NS(=O)(=O)N=C1Nc1cccc(C(=O)N(C)C)c1O)c1ccc(C)o1
CHEMBL473959 cxcr1_human Human No 8.2 Ki = 6 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
423 6 3 7 2.7 CN(C)C(=O)c1cccc(Nc2c(N[C@@H](c3ccco3)C(F)(F)F)c(=O)c2=O)c1O
CHEMBL491330 cxcr1_human Human No 8.2 Ki = 6 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
433 7 3 7 3.1 Cc1ccc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C(C)(F)F)o1
CHEMBL523984 cxcr1_human Human No 8.2 Ki = 6 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
433 7 3 7 3.1 Cc1coc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C(C)(F)F)c1
CHEMBL253921 cxcr1_human Human No 7.2 Ki = 61 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
447 4 3 7 2.5 CN(C)C(=O)c1cccc(NC2=NS(=O)(=O)N=C2N[C@@H](c2ccco2)C(C)(C)C)c1O
CHEMBL254942 cxcr1_human Human No 7.2 Ki = 61 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
445 8 3 8 4.6 CC[C@@H](Nc1n[s+]([O-])nc1Nc1cccc(C(=O)N(C)C)c1O)c1cc(C(C)C)co1
CHEMBL571141 cxcr1_human Human No 5.2 Ki = 6500 nM Bind
Displacement of [125I]IL-8 from human CXCR1 expressed in mouse BaF3 cells by liquid scintillation countingDisplacement of [125I]IL-8 from human CXCR1 expressed in mouse BaF3 cells by liquid scintillation counting
424 8 3 8 2.3 CCN(Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(OC)cc1
CHEMBL402076 cxcr1_human Human No 6.2 Ki = 652 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
461 5 3 6 2.7 CC(C)[C@@H](NC1=NS(=O)(=O)N=C1Nc1cccc(C(=O)N(C)C)c1O)c1cccc(F)c1
CHEMBL245699 cxcr1_human Human No 8.2 Ki = 7 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
411 8 3 7 3.2 CCc1coc([C@@H](CC)Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)c1
CHEMBL464013 cxcr1_human Human No 8.1 Ki = 7.5 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
469 7 3 8 5.2 CC[C@@H](Nc1nsnc1Nc1ccc(C(F)(F)F)c(C(=O)N(C)C)c1O)c1ccc(C)o1
CHEMBL396573 cxcr1_human Human No 8.1 Ki = 7.6 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
439 9 3 7 4.1 CCC(C)c1coc([C@@H](CC)Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)c1
CHEMBL518030 cxcr1_human Human No 7.1 Ki = 76 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
465 6 3 8 5.6 CN(C)C(=O)c1cccc(Nc2nsnc2N[C@@H](c2cc3ccccc3o2)C(C)(C)C)c1O
CHEMBL490689 cxcr1_human Human No 7.1 Ki = 78 nM Bind
Displacement of IL8 from CXCR1 receptorDisplacement of IL8 from CXCR1 receptor
443 6 3 7 5.0 CN(C)C(=O)c1cccc(Nc2nsnc2N[C@@H](c2cccc(F)c2)C(C)(C)C)c1O
CHEMBL518857 cxcr1_human Human No 8.1 Ki = 8 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
477 6 3 8 2.9 CN(C)C(=O)c1cccc(Nc2c(N[C@@H](c3ccc4c(c3)OCO4)C(F)(F)F)c(=O)c2=O)c1O
CHEMBL252288 cxcr1_human Human No 5.1 Ki = 8990 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
429 5 3 6 2.3 CC[C@@H](NC1=NS(=O)(=O)N=C1Nc1cccc(C(=O)N(C)C)c1O)c1ccccc1
CHEMBL515262 cxcr1_human Human No 8.1 Ki = 9 nM Bind
Binding affinity to CXCR1Binding affinity to CXCR1
437 6 3 7 3.1 Cc1ccc([C@H](Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C(F)(F)F)o1
CHEMBL245501 cxcr1_human Human No 8.1 Ki = 9 nM Bind
Displacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPADisplacement of [125I]IL8 from human CXCR1 expressed in CHO cells by SPA
397 7 3 7 2.9 CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)C)c2O)c(=O)c1=O)c1cc(C)co1
CHEMBL577075 cxcr1_human Human No 5.0 Ki = 9700 nM Bind
Displacement of [125I]IL-8 from human CXCR1 expressed in mouse BaF3 cells by liquid scintillation countingDisplacement of [125I]IL-8 from human CXCR1 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
CHEMBL4562140 cxcr1_human Human No 6.9 pIC50 = Bind
Measuring displacement of CXCL8 binding to recombinant CXCR1 in HEK cell membrane preparations.Measuring displacement of CXCL8 binding to recombinant CXCR1 in HEK cell membrane preparations.
476 10 3 8 1.5 OC[C@@H]([C@H](Oc1nc(SCc2cccc(c2F)F)nc(c1)NS(=O)(=O)N1CCC1)C)O
CHEMBL216981 cxcr1_human Human Yes 8.4 pIC50 = Funct
UnclassifiedUnclassified
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