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Discovery of 1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)urea (LY3009120) as a pan-RAF inhibitor with minimal paradoxical activation and activity against BRAF or RAS mutant tumor cells.

Autor: Henry JR; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Kaufman MD; ‡Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts 02451, United States., Peng SB; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Ahn YM; ‡Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts 02451, United States., Caldwell TM; ‡Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts 02451, United States., Vogeti L; ‡Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts 02451, United States., Telikepalli H; ‡Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts 02451, United States., Lu WP; ‡Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts 02451, United States., Hood MM; ‡Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts 02451, United States., Rutkoski TJ; ‡Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts 02451, United States., Smith BD; ‡Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts 02451, United States., Vogeti S; ‡Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts 02451, United States., Miller D; ‡Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts 02451, United States., Wise SC; ‡Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts 02451, United States., Chun L; §Emerald Biostructures, Bainbridge Island, Washington 98110, United States., Zhang X; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Zhang Y; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Kays L; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Hipskind PA; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Wrobleski AD; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Lobb KL; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Clay JM; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Cohen JD; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Walgren JL; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., McCann D; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Patel P; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Clawson DK; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Guo S; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Manglicmot D; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Groshong C; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Logan C; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Starling JJ; †Eli Lilly and Company, Indianapolis, Indiana 46285, United States., Flynn DL; ‡Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts 02451, United States.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2015 May 28; Vol. 58 (10), pp. 4165-79. Date of Electronic Publication: 2015 May 12.