Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 6, Issue 9, Pages 961-965Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ml500526p
Keywords
B-RAF; MAP; VEGF; serine/threonine kinases; tyrosine kinases
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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.
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