Identification of a selective inverse agonist for the orphan nuclear receptor estrogen-related receptor alpha

J Med Chem. 2004 Nov 4;47(23):5593-6. doi: 10.1021/jm049334f.

Abstract

The estrogen-related receptor alpha (ERRalpha) is an orphan receptor belonging to the nuclear receptor superfamily. The physiological role of ERRalpha has yet to be established primarily because of lack of a natural ligand. Herein, we describe the discovery of the first potent and selective inverse agonist of ERRalpha. Through in vitro and in vivo studies, these ligands will elucidate the endocrine signaling pathways mediated by ERRalpha including association with human disease states.

MeSH terms

  • Acrylamides / chemical synthesis*
  • Acrylamides / chemistry
  • Acrylamides / pharmacology
  • Animals
  • Benzaldehydes / chemical synthesis
  • Benzaldehydes / chemistry
  • Benzaldehydes / pharmacology
  • Cells, Cultured
  • Combinatorial Chemistry Techniques
  • Nitriles / chemical synthesis*
  • Nitriles / chemistry
  • Nitriles / pharmacology
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Receptors, Estrogen / agonists*
  • Receptors, Estrogen / physiology
  • Signal Transduction / drug effects
  • Stereoisomerism
  • Structure-Activity Relationship
  • Thiadiazoles / chemical synthesis*
  • Thiadiazoles / chemistry
  • Thiadiazoles / pharmacology
  • Thiazoles / chemical synthesis*
  • Thiazoles / chemistry
  • Thiazoles / pharmacology

Substances

  • Acrylamides
  • Benzaldehydes
  • ERRalpha estrogen-related receptor
  • Nitriles
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Estrogen
  • Thiadiazoles
  • Thiazoles
  • XCT790
  • vanillin