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BioAssay: AID 765050

Antagonist activity at human PPARdelta assessed as effect on TIPP-703-induced activity

It has been reported that ligand-mediated transcription factor peroxisome proliferator-activated receptor alpha (hPPARalpha) is involved in hepatitis C virus (HCV) RNA replication, whereas hPPARgamma is not, and the effect of hPPARdelta is unknown. Here, we show that hPPARdelta-selective antagonists effectively inhibit HCV RNA replication. We describe the design, synthesis and pharmacological more ..
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 Tested Compounds
 Tested Compounds
All(13)
 
 
Active(6)
 
 
Inactive(5)
 
 
Inconclusive(1)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(13)
 
 
Active(6)
 
 
Inactive(5)
 
 
Inconclusive(1)
 
 
Unspecified(1)
 
 
AID: 765050
Data Source: ChEMBL (976992)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2014-05-03
Modify Date: 2014-08-24

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Peroxisome proliferator-activated receptor delta; Short=PPAR-delta; AltName: Full=NUCI; AltName: Full=Nuclear hormone receptor 1; Short=NUC1; AltName: Full=Nuclear receptor subfamily 1 group C member 2; AltName: Full=Peroxisome proliferator-activated receptor beta; Short=PPAR-beta
Description ..   
Protein Family: The ligand binding domain of peroxisome proliferator-activated receptors
Comment ..   

Gene:PPARD     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 6
Description:
Title: Peroxisome proliferator-activated receptor delta antagonists inhibit hepatitis C virus RNA replication.

Abstract: It has been reported that ligand-mediated transcription factor peroxisome proliferator-activated receptor alpha (hPPARalpha) is involved in hepatitis C virus (HCV) RNA replication, whereas hPPARgamma is not, and the effect of hPPARdelta is unknown. Here, we show that hPPARdelta-selective antagonists effectively inhibit HCV RNA replication. We describe the design, synthesis and pharmacological evaluation of a series of biphenyl-4-carboxylic acid-type hPPARdelta antagonists, including previously reported compounds, as candidate anti-HCV agents. A representative compound (4c) dose-dependently inhibited HCV RNA replication (EC50 0.22 muM), while exhibiting relatively weak cytotoxicity to the host cells (CC50 2.5 muM). It also showed an additive and dose-dependent effect on the inhibition of HCV RNA replication by pegylated interferon alpha (Peg-IFNalpha) alone and by both Peg-IFNalpha and ribavirin (currently the clinical treatment of choice for HCV infection). Thus, combination of a hPPARdelta antagonist with current therapy may improve the efficacy of treatment for HCV infection.
(PMID: 23891183)
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
Show more
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 valueFloatμM
10IC50 standard valueIC50 standard valueFloatnM

* Activity Concentration.

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