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BioAssay: AID 776056

Inhibition of CCR5 (unknown origin) expressed in human HeLa cells assessed as inhibition of interaction of CHO cells expressing HIV-1 JRFLenv and HIV-1 Tat and human HeLa cells expressing CD4 after 20 hrs by beta-galactosidase reporter gene assay relative to AGP

The redesign of the previously reported thiophene-3-yl-methyl urea series, as a result of potential cardiotoxicity, was successfully accomplished, resulting in the identification of a novel potent series of CCR5 antagonists containing the imidazolidinylpiperidinyl scaffold. The main redesign criteria were to reduce the number of rotatable bonds and to maintain an acceptable lipophilicity to more ..
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 Tested Compounds
 Tested Compounds
All(14)
 
 
Unspecified(14)
 
 
 Tested Substances
 Tested Substances
All(14)
 
 
Unspecified(14)
 
 
 Related BioAssays
 Related BioAssays
AID: 776056
Data Source: ChEMBL (988286)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2014-05-03
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: Design of substituted imidazolidinylpiperidinylbenzoic acids as chemokine receptor 5 antagonists: potent inhibitors of R5 HIV-1 replication.

Abstract: The redesign of the previously reported thiophene-3-yl-methyl urea series, as a result of potential cardiotoxicity, was successfully accomplished, resulting in the identification of a novel potent series of CCR5 antagonists containing the imidazolidinylpiperidinyl scaffold. The main redesign criteria were to reduce the number of rotatable bonds and to maintain an acceptable lipophilicity to mitigate hERG inhibition. The structure-activity relationship (SAR) that was developed was used to identify compounds with the best pharmacological profile to inhibit HIV-1. As a result, five advanced compounds, 6d, 6e, 6i, 6h, and 6k, were further evaluated for receptor selectivity, antiviral activity against CCR5 using (R5) HIV-1 clinical isolates, and in vitro and in vivo safety. On the basis of these results, 6d and 6h were selected for further development.
(PMID: 24090135)
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
Assay Cell Type: CHO
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1FC activity commentFC activity commentString
2FC standard flagFC standard flagInteger
3FC qualifierFC qualifierString
4FC published valueFC published valueFloat
5FC standard valueFC standard valueFloat

Data Table (Concise)
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Classification
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