title: Identification of a selective inverse agonist for the orphan nuclear receptor estrogen-related receptor alpha.
abstract: The estrogen-related receptor alpha (ERRalpha) is an orphan receptor belonging to the nuclear receptor superfamily. The physiological role of ERRalpha has yet to be established primarily because of lack of a natural ligand. Herein, we describe the discovery of the first potent and selective inverse agonist of ERRalpha. Through in vitro and in vivo studies, these ligands will elucidate the endocrine signaling pathways mediated by ERRalpha including association with human disease states.
authors.affiliation: Department of Medicinal Chemistry, X-Ceptor Therapeutics, Inc., 4757 Nexus Center Drive, San Diego, California 92121, USA.
authors.forename: Brett B
authors.initials: BB
authors.lastname: Busch
authors.forename: William C
authors.initials: WC
authors.lastname: Stevens
authors.forename: Richard
authors.initials: R
authors.lastname: Martin
authors.forename: Peter
authors.initials: P
authors.lastname: Ordentlich
authors.forename: Sihong
authors.initials: S
authors.lastname: Zhou
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Sapp
authors.forename: Robert A
authors.initials: RA
authors.lastname: Horlick
authors.forename: Raju
authors.initials: R
authors.lastname: Mohan
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001547:Benzaldehydes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D020650:Combinatorial Chemistry Techniques; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000502:physiology; D011960:Receptors, Estrogen / Q000819:agonists* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D000178:Acrylamides; D001547:Benzaldehydes; D009570:Nitriles; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D013830:Thiadiazoles; D013844:Thiazoles; D000097983:ERRalpha Estrogen-Related Receptor; C488234:XCT790; C100058:vanillin