Discovery of dabrafenib: a selective inhibitor of Raf kinases with antitumor activity against B-Raf-driven tumors

TR Rheault, JC Stellwagen, GM Adjabeng…

Index: Rheault, Tara R.; Stellwagen, John C.; Adjabeng, George M.; Hornberger, Keith R.; Petrov, Kimberly G.; Waterson, Alex G.; Dickerson, Scott H.; Mook, Robert A.; Laquerre, Sylvie G.; King, Alastair J.; Rossanese, Olivia W.; Arnone, Marc R.; Smitheman, Kimberly N.; Kane-Carson, Laurie S.; Han, Chao; Moorthy, Ganesh S.; Moss, Katherine G.; Uehling, David E. ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 3 p. 358 - 362

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Citation Number: 46

Abstract

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 ...