Identification of an agonist ligand for estrogen-related receptors ERRbeta/gamma.
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.
Yu
Donna D
DD
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.
Forman
Barry Marc
BM
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
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