Identification of an agonist ligand for estrogen-related receptors ERRbeta/gamma

Bioorg Med Chem Lett. 2005 Mar 1;15(5):1311-3. doi: 10.1016/j.bmcl.2005.01.025.

Abstract

In order to develop agonist ligands that are specific for the estrogen-related receptors ERRbeta/gamma, a hydrazone with a 4-hydroxy group at one phenyl ring and a 4-diethylamino moiety at the other phenyl ring was synthesized. We demonstrate that compound 3 (DY131; N'-{(1E)-[4-(diethylamino)phenyl]methylene}-4-hydroxybenzohydrazide) effectively and selectively activates ERRbeta/gamma. DY131 had no effect on the structurally related receptors ERRalpha or the estrogen receptors alpha and beta (ERalpha/beta). This work defines a convenient synthesis for a novel and selective pharmacologic tool that can be used to elucidate the biological activities of ERRbeta/gamma.

MeSH terms

  • Animals
  • Cell Line
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • ERRalpha Estrogen-Related Receptor
  • Humans
  • Hydrazines / chemical synthesis*
  • Hydrazines / chemistry
  • Hydrazines / pharmacology
  • Hydrazones / chemical synthesis*
  • Hydrazones / chemistry
  • Hydrazones / pharmacology
  • Ligands
  • Mice
  • Molecular Mimicry
  • Molecular Structure
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Receptors, Estrogen / agonists*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / physiology
  • Structure-Activity Relationship
  • Transfection

Substances

  • Hydrazines
  • Hydrazones
  • Ligands
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Estrogen
  • ERRalpha Estrogen-Related Receptor
  • ESRRB protein, human
  • Esrrg protein, mouse
  • N'-((1E)-(4-(diethylamino)phenyl)methylene)-4-hydroxybenzohydrazide