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BioAssay: AID 601559

Displacement of 125I-MIP-1beta from human CCR5 receptor after 4 hrs by scintillation counting

We recently described ( J. Med. Chem. 2008 , 51 , 6538 - 6546 ) a novel class of CCR5 antagonists with strong anti-HIV potency. Herein, we detail SAR converting leads 1 and 2 to druglike molecules. The pivotal structural motif enabling this transition was the secondary sulfonamide substituent. Further fine-tuning of the substituent pattern in the sulfonamide paved the way to enhancing potency and bioavailability and minimizing hERG inhibition, resulting in discovery of clinical compound 122 (GSK163929). ..more
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 Tested Compounds
 Tested Compounds
All(26)
 
 
Active(20)
 
 
Inconclusive(2)
 
 
Unspecified(5)
 
 
 Tested Substances
 Tested Substances
All(27)
 
 
Active(20)
 
 
Inconclusive(2)
 
 
Unspecified(5)
 
 
AID: 601559
Data Source: ChEMBL (751710)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-02-15
Modify Date: 2014-08-23

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: 20
Description:
Title: Novel 4,4-disubstituted piperidine-based C-C chemokine receptor-5 inhibitors with high potency against human immunodeficiency virus-1 and an improved human ether-a-go-go related gene (hERG) profile.

Abstract: We recently described ( J. Med. Chem. 2008 , 51 , 6538 - 6546 ) a novel class of CCR5 antagonists with strong anti-HIV potency. Herein, we detail SAR converting leads 1 and 2 to druglike molecules. The pivotal structural motif enabling this transition was the secondary sulfonamide substituent. Further fine-tuning of the substituent pattern in the sulfonamide paved the way to enhancing potency and bioavailability and minimizing hERG inhibition, resulting in discovery of clinical compound 122 (GSK163929).
(PMID: 21539377)
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
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 binding domainsIC50 binding domainsString
12pIC50 activity commentpIC50 activity commentString
13pIC50 standard flagpIC50 standard flagInteger
14pIC50 qualifierpIC50 qualifierString
15pIC50 published valuepIC50 published valueFloat
16pIC50 standard valuepIC50 standard valueFloat
17pIC50 binding domainspIC50 binding domainsString

* Activity Concentration.

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