Document Report Card

ID: ALA2331286

Journal: ACS Med Chem Lett

Title: Discovery of Dabrafenib: A Selective Inhibitor of Raf Kinases with Antitumor Activity against B-Raf-Driven Tumors.

Authors: Rheault TR, Stellwagen JC, Adjabeng GM, Hornberger KR, Petrov KG, Waterson AG, Dickerson SH, Mook RA, Laquerre SG, King AJ, Rossanese OW, Arnone MR, Smitheman KN, Kane-Carson LS, Han C, Moorthy GS, Moss KG, Uehling DE.

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.

CiteXplore: 24900673

DOI: 10.1021/ml4000063