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BioAssay: AID 637686

Agonist activity at full length human PPARgamma1 transfected in human CHOK1 cells co expressing RXRalpha and PPRE after 1 day by luciferase reporter gene transactivation assay

Herein, we describe the design, synthesis, and structure-activity relationships of novel benzylpyrazole acylsulfonamides as non-thiazolidinedione (TZD), non-carboxylic-acid-based peroxisome proliferator-activated receptor (PPAR) gamma agonists. Docking model analysis of in-house weak agonist 2 bound to the reported PPARgamma ligand binding domain suggested that modification of the carboxylic acid more ..
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 Tested Compounds
 Tested Compounds
All(30)
 
 
Active(28)
 
 
Inactive(1)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(30)
 
 
Active(28)
 
 
Inactive(1)
 
 
Unspecified(1)
 
 
AID: 637686
Data Source: ChEMBL (795134)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-05-25

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Peroxisome proliferator-activated receptor gamma; Short=PPAR-gamma; AltName: Full=Nuclear receptor subfamily 1 group C member 3
Description ..   
Protein Family: The ligand binding domain of peroxisome proliferator-activated receptors
Comment ..   

Gene:PPARG     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 28
Description:
Title: A new class of non-thiazolidinedione, non-carboxylic-acid-based highly selective peroxisome proliferator-activated receptor (PPAR) gamma agonists: design and synthesis of benzylpyrazole acylsulfonamides.

Abstract: Herein, we describe the design, synthesis, and structure-activity relationships of novel benzylpyrazole acylsulfonamides as non-thiazolidinedione (TZD), non-carboxylic-acid-based peroxisome proliferator-activated receptor (PPAR) gamma agonists. Docking model analysis of in-house weak agonist 2 bound to the reported PPARgamma ligand binding domain suggested that modification of the carboxylic acid of 2 would help strengthen the interaction of 2 with the TZD pocket and afford non-carboxylic-acid-based agonists. In this study, we used an acylsulfonamide group as the ring-opening analog of TZD as an isosteric replacement of carboxylic acid moiety of 2; further, preliminary modification of the terminal alkyl chain on the sulfonyl group gave the lead compound 3c. Subsequent optimization of the resulting compound gave the potent agonists 25c, 30b, and 30c with high metabolic stability and significant antidiabetic activity. Further, we have described the difference in binding mode of the carboxylic-acid-based agonist 1 and acylsulfonamide 3d.
(PMID: 22209730)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
Assay Type: Functional

Assay Data Source: Scientific Literature

BAO: Assay Format: cell-based format

Assay Cell Type: CHO-K1

Target Type: Target is a single protein chain

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
7EC50 binding domainsEC50 binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
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