Identification of an agonist ligand for estrogen-related receptors ERRβ/γ

In order to develop agonist ligands that are specific for the estrogen-related receptors ERRβ/γ, 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 ERRβ/γ. DY131 had no effect on the structurally related receptors ERRα or the estrogen receptors α and β (ERα/β). This work defines a convenient synthesis for a novel and selective pharmacologic tool that can be used to elucidate the biological activities of ERRβ/γ.