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

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

  • ACS Med Chem Lett. 2015 Aug 3;6(9):961-5. doi: 10.1021/ml500526p.
Teresa E Williams 1,  Sharadha Subramanian 1,  Joelle Verhagen 1,  Christopher M McBride 1,  Abran Costales 1,  Leonard Sung 1,  William Antonios-McCrea 1,  Maureen McKenna 1,  Alicia K Louie 1,  Savithri Ramurthy 1,  Barry Levine 1,  Cynthia M Shafer 1,  Timothy Machajewski 1,  Paul A Renhowe 1,  Brent A Appleton 1,  Payman Amiri 1,  James Chou 1,  Darrin Stuart 1,  Kimberly Aardalen 1,  Daniel Poon 1
Affiliations

Affiliation

  • 1 Global Discovery Chemistry, Oncology and Exploratory Chemistry, Novartis Institutes for Biomedical Research , 5300 Chiron Way, Emeryville, California 94608, United States.
PMID: 26396681 DOI: 10.1021/ml500526p
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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