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BioAssay: AID 645347

Inhibition of human CCR2-mediated intracellular calcium mobilization by cell based assay

We report the identification of 13 (INCB3284) as a potent human CCR2 (hCCR2) antagonist. INCB3284 exhibited an IC50 of 3.7 nM in antagonism of monocyte chemoattractant protein-1 binding to hCCR2, an IC50 of 4.7 nM in antagonism of chemotaxis activity, an IC50 of 84 muM in inhibition of the hERG potassium current, a free fraction of 58% in protein binding, high selectivity over other chemokine more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Active(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Active(1)
 
 
AID: 645347
Data Source: ChEMBL (802795)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-08-24

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=C-C chemokine receptor type 2; Short=C-C CKR-2; Short=CC-CKR-2; Short=CCR-2; Short=CCR2; AltName: Full=Monocyte chemoattractant protein 1 receptor; Short=MCP-1-R; AltName: CD_antigen=CD192
Description ..   
Comment ..   

Gene:CCR2     Conserved Domain     Related Protein 3D Structures     More BioActivity Data..
BioActive Compound: 1
Description:
Title: Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist.

Abstract: We report the identification of 13 (INCB3284) as a potent human CCR2 (hCCR2) antagonist. INCB3284 exhibited an IC50 of 3.7 nM in antagonism of monocyte chemoattractant protein-1 binding to hCCR2, an IC50 of 4.7 nM in antagonism of chemotaxis activity, an IC50 of 84 muM in inhibition of the hERG potassium current, a free fraction of 58% in protein binding, high selectivity over other chemokine receptors and G-protein-coupled receptors, and acceptable oral bioavailability in rodents and primates. In human clinical trials, INCB3284 exhibited a pharmacokinetic profile suitable for once-a-day dosing (T 1/2 = 15 h).
(PMID: 24900329)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
BAO: Assay Format: cell-based format
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6IC50 activity commentIC50 activity commentString
7IC50 standard flagIC50 standard flagInteger
8IC50 qualifierIC50 qualifierString
9IC50 published valueIC50 published valueFloatnM
10IC50 standard valueIC50 standard valueFloatnM
11IC50 binding domainsIC50 binding domainsString

* Activity Concentration.

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
Classification
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