Identification of a selective inverse agonist for the orphan nuclear receptor estrogen-related receptor alpha.
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.
Busch
Brett B
BB
Department of Medicinal Chemistry, X-Ceptor Therapeutics, Inc., 4757 Nexus Center Drive, San Diego, California 92121, USA.
Stevens
William C
WC
Martin
Richard
R
Ordentlich
Peter
P
Zhou
Sihong
S
Sapp
Douglas W
DW
Horlick
Robert A
RA
Mohan
Raju
R
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
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