Discovery of XL335 (WAY-362450), a Highly Potent, Selective, and Orally Active Agonist of the Farnesoid X Receptor (FXR)

Citations Over TimeTop 10% of 2009 papers

Abstract

Azepino[4,5-b]indoles have been identified as potent agonists of the farnesoid X receptor (FXR). In vitro and in vivo optimization has led to the discovery of 6m (XL335, WAY-362450) as a potent, selective, and orally bioavailable FXR agonist (EC(50) = 4 nM, Eff = 149%). Oral administration of 6m to LDLR(-/-) mice results in lowering of cholesterol and triglycerides. Chronic administration in an atherosclerosis model results in significant reduction in aortic arch lesions.

Related Papers

• → Deciphering the nuclear bile acid receptor FXR paradigm(2010)282 cited
• → Design and identification of a new farnesoid X receptor (FXR) partial agonist by computational structure–activity relationship analysis: Ligand-induced H8 helix fluctuation in the ligand-binding domain of FXR may lead to partial agonism(2021)8 cited
• → Design, synthesis, and biological studies of novel 3-benzamidobenzoic acid derivatives as farnesoid X receptor partial agonist(2020)12 cited
• → Design, synthesis and structure-activity relationship studies of novel partial FXR agonists for the treatment of fatty liver(2020)5 cited
• → Human fat cell alpha-2 adrenoceptors. II. Comparative study of partial and full agonist binding parameters using [3H]clonidine and [3H]UK-14,304.(1989)12 cited