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

Basic Information

ID: ALA3632535

Journal: ACS Med Chem Lett

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

Authors: Williams TE, Subramanian S, Verhagen J, McBride CM, Costales A, Sung L, Antonios-McCrea W, McKenna M, Louie AK, Ramurthy S, Levine B, Shafer CM, Machajewski T, Renhowe PA, Appleton BA, Amiri P, Chou J, Stuart D, Aardalen K, Poon D.

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.

CiteXplore: 26396681

DOI: 10.1021/ml500526p

Patent ID: