On the intractability of estrogen-related receptor alpha as a target for activation by small molecules

J Med Chem. 2007 Dec 27;50(26):6722-4. doi: 10.1021/jm7012387. Epub 2007 Dec 4.

Abstract

The estrogen-related receptor alpha (ERRalpha) is a potential target for activation in the treatment of metabolic disease. To date, no small-molecule agonists of ERRalpha have been identified despite several high-throughput screening campaigns. We describe the synthesis and profiling of a small array of compounds designed on the basis of a previously reported agonist-bound crystal structure of the closely related receptor ERRgamma. The results suggest that ERRalpha may be intractable as a direct target for pharmacologic activation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Drug Inverse Agonism
  • Fluorescence Resonance Energy Transfer
  • HeLa Cells
  • Humans
  • Hydrazones / chemical synthesis
  • Hydrazones / chemistry*
  • Hydrazones / pharmacology*
  • Receptors, Estrogen / agonists*
  • Receptors, Estrogen / antagonists & inhibitors
  • Receptors, Estrogen / chemistry*

Substances

  • ERRalpha estrogen-related receptor
  • Hydrazones
  • Receptors, Estrogen