| Literature DB >> 24900673 |
Tara R Rheault1, John C Stellwagen1, George M Adjabeng1, Keith R Hornberger1, Kimberly G Petrov1, Alex G Waterson1, Scott H Dickerson2, Robert A Mook1, Sylvie G Laquerre3, Alastair J King3, Olivia W Rossanese3, Marc R Arnone3, Kimberly N Smitheman3, Laurie S Kane-Carson4, Chao Han3, Ganesh S Moorthy3, Katherine G Moss3, David E Uehling1.
Abstract
Hyperactive signaling of the MAP kinase pathway resulting from the constitutively active B-Raf(V600E) mutated enzyme has been observed in a number of human tumors, including melanomas. Herein we report the discovery and biological evaluation of GSK2118436, a selective inhibitor of Raf kinases with potent in vitro activity in oncogenic B-Raf-driven melanoma and colorectal carcinoma cells and robust in vivo antitumor and pharmacodynamic activity in mouse models of B-Raf(V600E) human melanoma. GSK2118436 was identified as a development candidate, and early clinical results have shown significant activity in patients with B-Raf mutant melanoma.Entities:
Keywords: B-Raf; GSK2118436; MAP kinase; dabrafenib; melanoma
Year: 2013 PMID： 24900673 PMCID： PMC4027516 DOI： 10.1021/ml4000063
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345