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ACS Med Chem Lett. 2015 Aug 3;6(9):961-5. doi: 10.1021/ml500526p. eCollection 2015 Sep 10.

Discovery of RAF265: A Potent mut-B-RAF Inhibitor for the Treatment of Metastatic Melanoma.

Author information

1
Global Discovery Chemistry, Oncology and Exploratory Chemistry, Novartis Institutes for Biomedical Research , 5300 Chiron Way, Emeryville, California 94608, United States.

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 pharmacokinetic/pharmacodynamic (PKPD) and PD-efficacy relationships led to the identification of RAF265, 1, which has advanced into clinical trials.

KEYWORDS:

B-RAF; MAP; VEGF; serine/threonine kinases; tyrosine kinases

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