Identification of a Selective Inverse Agonist for the Orphan Nuclear Receptor Estrogen-Related Receptor α

• Published in: Journal of medicinal chemistry Vol. 47; no. 23; pp. 5593 - 5596
• Main Authors: Busch, Brett B, Stevens, William C, Martin, Richard, Ordentlich, Peter, Zhou, Sihong, Sapp, Douglas W, Horlick, Robert A, Mohan, Raju
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 04-11-2004
• Subjects: Acrylamides - chemical synthesis; Acrylamides - chemistry; Acrylamides - pharmacology; Animals; Benzaldehydes - chemical synthesis; Benzaldehydes - chemistry; Benzaldehydes - pharmacology; Biological and medical sciences; Cells, Cultured; Combinatorial Chemistry Techniques; ERRalpha Estrogen-Related Receptor; Hormones. Endocrine system; Medical sciences; Nitriles - chemical synthesis; Nitriles - chemistry; Nitriles - pharmacology; Pharmacology. Drug treatments; Receptors, Cytoplasmic and Nuclear - agonists; Receptors, Cytoplasmic and Nuclear - physiology; Receptors, Estrogen - agonists; Receptors, Estrogen - physiology; Signal Transduction - drug effects; Stereoisomerism; Structure-Activity Relationship; Thiadiazoles - chemical synthesis; Thiadiazoles - chemistry; Thiadiazoles - pharmacology; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; Sulfur nitrogen heterocycle; Five membered ring; Nuclear receptor; Nitrile; Benzene derivatives; Selectivity; Thiadiazole derivatives; In vitro; Estrogen receptor α; Signal transduction; Cell line; Structure activity relation; Inverse agonist; Vinylic compound; Fluorine Organic compounds; Chemical synthesis; Orphan receptor
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm049334f

The estrogen-related receptor α (ERRα) is an orphan receptor belonging to the nuclear receptor superfamily. The physiological role of ERRα 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 ERRα. Through in vitro and in vivo studies, these ligands will elucidate the endocrine signaling pathways mediated by ERRα including association with human disease states.