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BioAssay: AID 716302

Ratio of ZnPhe EC50 to compound EC50 for human CCR5 transfected in COS7 cells coexpressing chimeric Gqi4myr assessed as IP3 turnover by liquid scintillation counting analysis

Among 18 human chemokine receptors, CCR1, CCR4, CCR5, and CCR8 were activated by metal ion Zn(II) or Cu(II) in complex with 2,2'-bipyridine or 1,10-phenanthroline with similar potencies (EC(50) from 3.9 to 172 muM). Besides being agonists, they acted as selective allosteric enhancers of CCL3. These actions were dependent on a conserved glutamic acid at TM-7 (VII:06/7.39). A screening of 20 more ..
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 Tested Compounds
 Tested Compounds
All(7)
 
 
Unspecified(7)
 
 
 Tested Substances
 Tested Substances
All(7)
 
 
Unspecified(7)
 
 
 Related BioAssays
 Related BioAssays
AID: 716302
Data Source: ChEMBL (884045)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-06-29
Modify Date: 2014-05-26

Data Table ( Complete ):           All
Target
Sequence: RecName: Full=C-C chemokine receptor type 5; Short=C-C CKR-5; Short=CC-CKR-5; Short=CCR-5; Short=CCR5; AltName: Full=CHEMR13; AltName: Full=HIV-1 fusion coreceptor; AltName: CD_antigen=CD195
Description ..   
Comment ..   

Gene:CCR5     Conserved Domain     Related Protein 3D Structures     More BioActivity Data..
Tested Compounds:
Description:
Title: Modulation in selectivity and allosteric properties of small-molecule ligands for CC-chemokine receptors.

Abstract: Among 18 human chemokine receptors, CCR1, CCR4, CCR5, and CCR8 were activated by metal ion Zn(II) or Cu(II) in complex with 2,2'-bipyridine or 1,10-phenanthroline with similar potencies (EC(50) from 3.9 to 172 muM). Besides being agonists, they acted as selective allosteric enhancers of CCL3. These actions were dependent on a conserved glutamic acid at TM-7 (VII:06/7.39). A screening of 20 chelator analogues in complex with Zn(II) identified compounds with increased potencies, with 7 reaching highest potency at CCR1 (EC(50) of 0.85 muM), 20 at CCR8 (0.39 muM), and 8 at CCR5 (1.0 muM). Altered selectivity for CCR1 and CCR8 over CCR5 (11, 12) and a receptor-dependent separation of allosteric from intrinsic properties were achieved (20). The pocket similarities of CCR1 and CCR8, contrary to CCR5 as proposed by the ligand screen, were elaborated by computational modeling. These studies facilitate exploration of chemokine receptors as possible targets for therapeutic intervention.
(PMID: 22957890)
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: cell-based format

Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ratio EC50 activity commentRatio EC50 activity commentString
2Ratio EC50 standard flagRatio EC50 standard flagInteger
3Ratio EC50 qualifierRatio EC50 qualifierString
4Ratio EC50 published valueRatio EC50 published valueFloat
5Ratio EC50 standard valueRatio EC50 standard valueFloat

Data Table (Concise)
Classification
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