Bookmark and Share
BioAssay: AID 716295

Allosteric modulation at human CCR5 transfected in COS7 cells coexpressing chimeric Gqi4myr assessed as [3H]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(22)
 
 
Active(12)
 
 
Unspecified(10)
 
 
 Tested Substances
 Tested Substances
All(22)
 
 
Active(12)
 
 
Unspecified(10)
 
 
AID: 716295
Data Source: ChEMBL (884038)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-06-29
Modify Date: 2014-08-25

Data Table ( Complete ):           View Active Data    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..
BioActive Compounds: 12
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)
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
Show more
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1EC50*EC50 PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6EC50 activity commentEC50 activity commentString
7EC50 standard flagEC50 standard flagInteger
8EC50 qualifierEC50 qualifierString
9EC50 published valueEC50 published valueFloat
10EC50 standard valueEC50 standard valueFloatnM
11EC50 data validityEC50 data validityString
12EC50 binding domainsEC50 binding domainsString
13EC50 activity commentEC50 activity commentString
14EC50 standard flagEC50 standard flagInteger
15EC50 qualifierEC50 qualifierString
16EC50 published valueEC50 published valueFloatμM
17EC50 standard valueEC50 standard valueFloatnM
18EC50 data validityEC50 data validityString
19EC50 binding domainsEC50 binding domainsString

* Activity Concentration.

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