Download MendeleyDiscovery of XL335 (WAY-362450), a highly potent, selective, and orally active agonist of the farnesoid X receptor (FXR).
Flatt, B., Martin, R., Wang, T.L., Mahaney, P., Murphy, B., Gu, X.H., Foster, P., Li, J., Pircher, P., Petrowski, M., Schulman, I., Westin, S., Wrobel, J., Yan, G., Bischoff, E., Daige, C., Mohan, R.(2009) J Med Chem 52: 904-907
- PubMed: 19159286
- DOI: https://doi.org/10.1021/jm8014124
- Primary Citation of Related Structures:
3FLI - PubMed 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.
Organizational Affiliation:
Department of Medicinal Chemistry, Exelixis Inc., 4757 Nexus Centre Drive, San Diego, California 92121, USA. [email protected]
