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BioAssay: AID 637692

Binding affinity to PPARdelta at 10 uM by competitive binding 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
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Inactive(4)
 
 
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AID: 637692
Data Source: ChEMBL (795140)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-08-23

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Tested Compounds:
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
Putative Target:
ChEMBL Target ID: 12227
Target Type: SINGLE PROTEIN
Pref Name: Peroxisome proliferator-activated receptor delta
Synonyms: NUC1;NUCI;Nuclear hormone receptor 1;Nuclear receptor subfamily 1 group C member 2;Peroxisome proliferator-activated receptor beta;Peroxisome proliferator-activated receptor delta;PPAR-beta;PPAR-delta;
Gene Name: NR1C2 ;PPARB;PPARD;
Protein Accession: Q03181;
Protein GI: 417522;
Organism: Homo sapiens
Tax ID: 9606
Target Classification: transcription factor nuclear receptor nr1 nr1c nr1c2
Confidence: Homologous single protein target assigned
Relationship Type: Homologous protein target assigned
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Assay Data Source: Scientific Literature
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Activity activity commentActivity activity commentString
2Activity standard flagActivity standard flagInteger
3Activity qualifierActivity qualifierString
4Activity published valueActivity published valueFloat
5Activity standard valueActivity standard valueFloat

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