title: Identification of an agonist ligand for estrogen-related receptors ERRbeta/gamma.
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.
authors.affiliation: Department of Gene regulation and Drug Discovery, The Beckman Research Institute, The City of Hope National Medical Center, The Gonda Diabetes and Genetic Research Center, Duarte, CA 91010, USA.
authors.forename: Donna D
authors.initials: DD
authors.lastname: Yu
authors.forename: Barry Marc
authors.initials: BM
authors.lastname: Forman
mesh_terms: D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D018716:Molecular Mimicry; D015394:Molecular Structure; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000235:genetics / Q000502:physiology; D011960:Receptors, Estrogen / Q000819:agonists* / Q000235:genetics / Q000502:physiology; D013329:Structure-Activity Relationship; D014162:Transfection; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D006834:Hydrazines; D006835:Hydrazones; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor; C490918:ESRRB protein, human; C490916:Esrrg protein, mouse; C501618:N'-((1E)-(4-(diethylamino)phenyl)methylene)-4-hydroxybenzohydrazide