Identification and characterization of 4-chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide (GSK3787), a selective and irreversible peroxisome proliferator-activated receptor delta (PPARdelta) antagonist

  • J Med Chem. 2010 Feb 25;53(4):1857-61. doi: 10.1021/jm900464j.
Barry G Shearer  1 ,  Robert W Wiethe ,  Adam Ashe ,  Andrew N Billin ,  James M Way ,  Thomas B Stanley ,  Craig D Wagner ,  Robert X Xu ,  Lisa M Leesnitzer ,  Raymond V Merrihew ,  Todd W Shearer ,  Michael R Jeune ,  John C Ulrich ,  Timothy M Willson
Affiliations
  • 1. Department of Metabolic Chemistry, Metabolic Diseases Centre of Excellence for Drug Discovery, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA. [email protected]
PMID: 20128594 DOI: 10.1021/jm900464j
Abstract

4-Chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide 3 (GSK3787) was identified as a potent and selective ligand for PPARdelta with good pharmacokinetic properties. A detailed binding study using mass spectral analysis confirmed covalent binding to Cys249 within the PPARdelta binding pocket. Gene expression studies showed that pyridylsulfone 3 antagonized the transcriptional activity of PPARdelta and inhibited basal CPT1a gene transcription. Compound 3 is a PPARdelta antagonist with utility as a tool to elucidate PPARdelta Cell Biology and pharmacology.

Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15577
    GSK3787
    99.94%, PPARδ Antagonist
    target: PPAR
    Research Areas: Cancer