Discovery of RAF 265: A Potent mut-B-RAF Inhibitor for the Treatment of Metastatic Melanoma
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 |
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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 |