Bookmark and Share
BioAssay: AID 716301

Ratio of ZnBip 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 ..
_
   
 Tested Compounds
 Tested Compounds
All(4)
 
 
Unspecified(4)
 
 
 Tested Substances
 Tested Substances
All(4)
 
 
Unspecified(4)
 
 
 Related BioAssays
 Related BioAssays
AID: 716301
Data Source: ChEMBL (884044)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-06-29
Modify Date: 2014-08-25

Data Table ( Complete ):           View All Data
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 - 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
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)
Data Table ( Complete ):     View All Data
Classification
PageFrom: