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BioAssay: AID 716287

Displacement of [125I]-CCL3 from human CCR5 transfected in COS7 cells coexpressing chimeric Gqi4myr after 3 hrs

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(22)
 
 
Active(3)
 
 
Inactive(3)
 
 
Inconclusive(2)
 
 
Unspecified(14)
 
 
 Tested Substances
 Tested Substances
All(22)
 
 
Active(3)
 
 
Inactive(3)
 
 
Inconclusive(2)
 
 
Unspecified(14)
 
 
AID: 716287
Data Source: ChEMBL (884030)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-06-29
Modify Date: 2014-05-26

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: 3
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
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: cell-based format

Target Type: Target is a single protein chain

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 valueFloat
10IC50 standard valueIC50 standard valueFloatnM
11IC50 data validityIC50 data validityString
12IC50 binding domainsIC50 binding domainsString
13IC50 activity commentIC50 activity commentString
14IC50 standard flagIC50 standard flagInteger
15IC50 qualifierIC50 qualifierString
16IC50 published valueIC50 published valueFloatμM
17IC50 standard valueIC50 standard valueFloatnM
18IC50 data validityIC50 data validityString
19IC50 binding domainsIC50 binding domainsString
20pIC50 activity commentpIC50 activity commentString
21pIC50 standard flagpIC50 standard flagInteger
22pIC50 qualifierpIC50 qualifierString
23pIC50 published valuepIC50 published valueFloat
24pIC50 standard valuepIC50 standard valueFloat
25pIC50 data validitypIC50 data validityString
26pIC50 binding domainspIC50 binding domainsString

* Activity Concentration.

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