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10.1021/ml4000063

http://scihub22266oqcxt.onion/10.1021/ml4000063
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suck abstract from ncbi


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pmid24900673
      ACS+Med+Chem+Lett 2013 ; 4 (3 ): 358-62
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  • Discovery of Dabrafenib: A Selective Inhibitor of Raf Kinases with Antitumor Activity against B-Raf-Driven Tumors #MMPMID24900673
  • Rheault TR ; Stellwagen JC ; Adjabeng GM ; Hornberger KR ; Petrov KG ; Waterson AG ; Dickerson SH ; Mook RA Jr ; Laquerre SG ; King AJ ; Rossanese OW ; Arnone MR ; Smitheman KN ; Kane-Carson LS ; Han C ; Moorthy GS ; Moss KG ; Uehling DE
  • ACS Med Chem Lett 2013[Mar]; 4 (3 ): 358-62 PMID24900673 show ga
  • 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.
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