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BioAssay: AID 264214

Inhibition of CCR7 expressed in CHO cells at 10 uM

We incorporated various polar groups into previously described piperidine-4-carboxamide CCR5 antagonists to improve their metabolic stability in human hepatic microsomes. Introducing a carbamoyl group into the phenyl ring of the 4-benzylpiperidine moiety afforded the less lipophilic compound 5f, which possessed both high metabolic stability and good inhibitory activity of HIV-1 envelope-mediated more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Inactive(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Inactive(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 264214
Data Source: ChEMBL (351950)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-24
Modify Date: 2013-11-18

Data Table ( Complete ):           All
Target
Sequence: RecName: Full=C-C chemokine receptor type 7; Short=C-C CKR-7; Short=CC-CKR-7; Short=CCR-7; AltName: Full=BLR2; AltName: Full=CDw197; AltName: Full=Epstein-Barr virus-induced G-protein coupled receptor 1; Short=EBI1; Short=EBV-induced G-protein coupled receptor 1; AltName: Full=MIP-3 beta receptor; AltName: CD_antigen=CD197; Flags: Precursor
Description ..   
Comment ..   

Gene:CCR7     Conserved Domain     Related Protein 3D Structures     More BioActivity Data..
Tested Compound:
Description:
Title: Discovery of a piperidine-4-carboxamide CCR5 antagonist (TAK-220) with highly potent Anti-HIV-1 activity.

Abstract: We incorporated various polar groups into previously described piperidine-4-carboxamide CCR5 antagonists to improve their metabolic stability in human hepatic microsomes. Introducing a carbamoyl group into the phenyl ring of the 4-benzylpiperidine moiety afforded the less lipophilic compound 5f, which possessed both high metabolic stability and good inhibitory activity of HIV-1 envelope-mediated membrane fusion (IC(50) = 5.8 nM). Further optimization to increase potency led to the discovery of 1-acetyl-N-{3-[4-(4-carbamoylbenzyl)piperidin-1-yl]propyl}-N-(3-chloro-4-methylphenyl)piperidine-4-carboxamide (5m, TAK-220), which showed high CCR5 binding affinity (IC(50) = 3.5 nM) and potent inhibition of membrane fusion (IC(50) = 0.42 nM), as well as good metabolic stability. Compound 5m strongly inhibited the replication of CCR5-using HIV-1 clinical isolates in human peripheral blood mononuclear cells (mean EC(50) = 1.1 nM, EC(90) = 13 nM) and exhibited a good pharmacokinetic profile in monkeys (BA = 29%). This compound has been chosen as a clinical candidate for further development.
(PMID: 16640339)
Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Assay Cell Type: CHO

ChEMBL Target ID: 100434

ChEMBL Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Inhibition activity commentInhibition activity commentString
2Inhibition standard flagInhibition standard flagInteger
3Inhibition qualifierInhibition qualifierString
4Inhibition published valueInhibition published valueFloat
5Inhibition standard valueInhibition standard valueFloat

Data Table (Concise)
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