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BioAssay: AID 248424

Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear cells

The CXC chemokine CXCL8/IL-8 plays a major role in the activation and recruitment of polymorphonuclear (PMN) cells at inflammatory sites. CXCL8 activates PMNs by binding the seven-transmembrane (7-TM) G-protein-coupled receptors CXC chemokine receptor 1 (CXCR1) and CXC chemokine receptor 2 (CXCR2). (R)-Ketoprofen (1) was previously reported to be a potent and specific noncompetitive inhibitor of more ..
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 Tested Compounds
 Tested Compounds
All(8)
 
 
Active(7)
 
 
Inactive(1)
 
 
 Tested Substances
 Tested Substances
All(8)
 
 
Active(7)
 
 
Inactive(1)
 
 
AID: 248424
Data Source: ChEMBL (312518)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-24
Modify Date: 2014-05-20

Data Table ( Complete ):           Active    All
Targets
Sequence: RecName: Full=C-X-C chemokine receptor type 2; Short=CXC-R2; Short=CXCR-2; AltName: Full=CDw128b; AltName: Full=GRO/MGSA receptor; AltName: Full=High affinity interleukin-8 receptor B; Short=IL-8R B; AltName: Full=IL-8 receptor type 2; AltName: CD_antigen=CD182
Description ..   
Comment ..   

Gene:CXCR2     Conserved Domain     Related Protein 3D Structures     More BioActivity Data..

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BioActive Compounds: 7
Description:
Title: 2-Arylpropionic CXC chemokine receptor 1 (CXCR1) ligands as novel noncompetitive CXCL8 inhibitors.

Abstract: The CXC chemokine CXCL8/IL-8 plays a major role in the activation and recruitment of polymorphonuclear (PMN) cells at inflammatory sites. CXCL8 activates PMNs by binding the seven-transmembrane (7-TM) G-protein-coupled receptors CXC chemokine receptor 1 (CXCR1) and CXC chemokine receptor 2 (CXCR2). (R)-Ketoprofen (1) was previously reported to be a potent and specific noncompetitive inhibitor of CXCL8-induced human PMNs chemotaxis. We report here molecular modeling studies showing a putative interaction site of 1 in the TM region of CXCR1. The binding model was confirmed by alanine scanning mutagenesis and photoaffinity labeling experiments. The molecular model driven medicinal chemistry optimization of 1 led to a new class of potent and specific inhibitors of CXCL8 biological activity. Among these, repertaxin (13) was selected as a clinical candidate drug for prevention of post-ischemia reperfusion injury.
(PMID: 15974585)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
Assay Type: Functional

Assay Data Source: Scientific Literature

BAO: Assay Format: cell-based format

Target Type: Target is a group of closely related proteins

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2IC50 activity commentIC50 activity commentString
3IC50 standard flagIC50 standard flagInteger
4IC50 qualifierIC50 qualifierString
5IC50 published valueIC50 published valueFloatnM
6IC50 standard valueIC50 standard valueFloatnM

* Activity Concentration.

Data Table (Concise)
Classification
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