Identification and characterization of a selective peroxisome proliferator-activated receptor beta/delta (NR1C2) antagonist

Mol Endocrinol. 2008 Feb;22(2):523-9. doi: 10.1210/me.2007-0190. Epub 2007 Nov 1.

Abstract

The identification of small molecule ligands for the peroxisome proliferator-activated receptors (PPARs) has been instrumental in elucidating their biological roles. In particular, agonists have been the focus of much of the research in the field with relatively few antagonists being described and all of those being selective for PPARalpha or PPARgamma. The comparison of these agonist and antagonist ligands in cellular and animal systems has often led to surprising results and new insights into the biology of the PPARs. The PPARbeta/delta receptor is emerging as an important regulator of energy metabolism, inflammation, and cell growth and differentiation; however, only agonist ligands have been described for this receptor thus far. Here we describe the first report of a PPARbeta/delta small molecule antagonist ligand. This antagonist ligand will be a useful tool for elucidating the biological roles of PPARbeta/delta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • Dose-Response Relationship, Drug
  • Fatty Acids / metabolism
  • Fluorescence Resonance Energy Transfer
  • Gene Expression Regulation / drug effects
  • Humans
  • Ligands*
  • Molecular Structure
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Oxidation-Reduction / drug effects
  • PPAR delta / antagonists & inhibitors*
  • PPAR-beta / antagonists & inhibitors*
  • Sulfones / chemistry
  • Sulfones / pharmacology
  • Thiazoles / chemistry
  • Thiazoles / pharmacology
  • Thiophenes / chemistry
  • Thiophenes / pharmacology

Substances

  • Fatty Acids
  • GSK0660
  • GW0742
  • Ligands
  • PPAR delta
  • PPAR-beta
  • Sulfones
  • Thiazoles
  • Thiophenes