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

Abrogation of errant signaling along the MAPK pathway through the inhibition of B- RAF kinaseis a validated approach for the treatment of pathway-dependent cancers. We report the development of imidazo- benzimidazolesas 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.