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 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 pharma...

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Published in:ACS medicinal chemistry letters 2015-09, Vol.6 (9), p.961-965
Main Authors: Williams, Teresa E, 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 M, Machajewski, Timothy, Renhowe, Paul A, Appleton, Brent A, Amiri, Payman, Chou, James, Stuart, Darrin, Aardalen, Kimberly, Poon, Daniel
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cited_by cdi_FETCH-LOGICAL-a471t-e41a41c5cf640346ae2452db39729ab5bebaee190aaf4d6c32afe13aef574d8e3
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container_end_page 965
container_issue 9
container_start_page 961
container_title ACS medicinal chemistry letters
container_volume 6
creator Williams, Teresa E
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 M
Machajewski, Timothy
Renhowe, Paul A
Appleton, Brent A
Amiri, Payman
Chou, James
Stuart, Darrin
Aardalen, Kimberly
Poon, Daniel
description 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.
doi_str_mv 10.1021/ml500526p
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subjects Letter
title Discovery of RAF265: A Potent mut-B-RAF Inhibitor for the Treatment of Metastatic Melanoma
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