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BioAssay: AID 658317

Transactivation of human PPARalpha expressed in african green monkey COS1 cells after 1 day by luciferase reporter gene assay

In our search for a novel class of non-TZD, non-carboxylic acid peroxisome proliferator-activated receptor (PPAR) gamma agonists, we explored alternative lipophilic templates to replace benzylpyrazole core of the previously reported agonist 1. Introduction of a pentylsulfonamide group into arylpropionic acids derived from previous in-house PPARgamma ligands succeeded in the identification of more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Unspecified(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 658317
Data Source: ChEMBL (815389)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-05-16
Modify Date: 2014-08-25

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

Gene:PPARA     Related Protein 3D Structures     More BioActivity Data..
Tested Compound:
Description:
Title: Structure-activity relationships and key structural feature of pyridyloxybenzene-acylsulfonamides as new, potent, and selective peroxisome proliferator-activated receptor (PPAR) gamma Agonists.

Abstract: In our search for a novel class of non-TZD, non-carboxylic acid peroxisome proliferator-activated receptor (PPAR) gamma agonists, we explored alternative lipophilic templates to replace benzylpyrazole core of the previously reported agonist 1. Introduction of a pentylsulfonamide group into arylpropionic acids derived from previous in-house PPARgamma ligands succeeded in the identification of 2-pyridyloxybenzene-acylsulfonamide 2 as a lead compound. Docking studies of compound 2 suggested that a substituent para to the central benzene ring should be incorporated to effectively fill the Y-shaped cavity of the PPARgamma ligand-binding domain (LBD). This strategy led to significant improvement of PPARgamma activity. Further optimization to balance in vitro activity and metabolic stability allowed the discovery of the potent, selective and orally efficacious PPARgamma agonist 8f. Structure-activity relationship study as well as detailed analysis of the binding mode of 8f to the PPARgamma-LBD revealed the essential structural features of this series of ligands.
(PMID: 22503460)
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 Test Type: In vitro
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1EC50*EC50 PubChem standard valueFloatμM
2EC50 activity commentEC50 activity commentString
3EC50 standard flagEC50 standard flagInteger
4EC50 qualifierEC50 qualifierString
5EC50 published valueEC50 published valueFloatnM
6EC50 standard valueEC50 standard valueFloatnM

* Activity Concentration.

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