Poon, Daniel, Williams, Teresa, Subramanian, Sharadha, Verhagen, Joelle, McBride, Christopher M., Costales, Abran, Sung, Leonard, Antonios-McCrea, William, McKenna, Maureen, Louie, Alicia K., Ramurthy, Savithri, Levine, Barry, Shafer, Cynthia, Machajewski, Timothy, Renhowe, Paul A., Appleton, Brent A., Amiri, Payman, Chou, James, Stuart, Darrin and Aardalen, Kimberly (2015) Discovery of RAF 265: A Potent mut-B-RAF Inhibitor for the Treatment of Metastatic Melanoma. ACS Medicinal Chemistry Letters.

Abstract

Abrogation of errant signaling along the MAPK pathway through the inhibition of B-RAF kinase is a validated approach for the treatment of pathway dependent cancers. We report the development of imidazo-benzimidazoles as potent B-RAF inhibitors. Robust in vivo efficacy coupled with correlating PKPD and PD-efficacy relationships led to the identification of RAF265, 1, which has advanced into clinical trials.

Item Type:	Article
Keywords:	RAF, VEGF, serine-threonine kinases, tyrosine kinases, MAPK
Date Deposited:	09 May 2016 23:45
Last Modified:	09 May 2016 23:45
URI:	https://oak.novartis.com/id/eprint/24218