Discovery of dabrafenib: A selective inhibitor of Raf Kinases with antitumor activity against B-Raf-driven tumors

Journal Article (Journal Article)

Hyperactive signaling of the MAP kinase pathway resulting from the constitutively active B-RafV600E 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-RafV600E human melanoma. GSK2118436 was identified as a development candidate, and early clinical results have shown significant activity in patients with B-Raf mutant melanoma. © 2013 American Chemical Society.

Full Text

Duke Authors

Cited 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

Published Date

  • March 14, 2013

Published In

Volume / Issue

  • 4 / 3

Start / End Page

  • 358 - 362

Electronic International Standard Serial Number (EISSN)

  • 1948-5875

Digital Object Identifier (DOI)

  • 10.1021/ml4000063

Citation Source

  • Scopus