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

Journal of Medicinal Chemistry

Volumn 58, Issue 10, 2015, Pages 4165-4179

  Henry, James R ^a   Kaufman, Michael D ^b   Peng, Sheng Bin ^a   Ahn, Yu Mi ^b   Caldwell, Timothy M ^b   Vogeti, Lakshminarayana ^b   Telikepalli, Hanumaiah ^b   Lu, Wei Ping ^b   Hood, Molly M ^b   Rutkoski, Thomas J ^b   Smith, Bryan D ^b   Vogeti, Subha ^b   Miller, David ^b   Wise, Scott C ^b   Chun, Lawrence ^c   Zhang, Xiaoyi ^a   Zhang, Youyan ^a   Kays, Lisa ^a   Hipskind, Philip A ^a   Wrobleski, Aaron D ^a   Lobb, Karen L ^a   Clay, Julia M ^a   Cohen, Jeffrey D ^a   Walgren, Jennie L ^a   McCann, Denis ^a   Patel, Phenil ^a   Clawson, David K ^a   Guo, Sherry ^a   Manglicmot, Danalyn ^a   Groshong, Chris ^a   Logan, Cheyenne ^a   Starling, James J ^a   Flynn, Daniel L ^b   more..

^a ELI LILLY AND COMPANY   (United States)

^b Deciphera Pharmaceuticals LLC   (United States)

^c Emerald Biostructures ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (3,3 DIMETHYLBUTYL) 3 [FLUORO 4 METHYL 5 [7 METHYL 2 (METHYLAMINO)PYRIDO[2,3 D]PYRIMIDIN 6 YL)PHENYL]UREA; B RAF KINASE; B RAF KINASE INHIBITOR; RAS PROTEIN; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; BRAF PROTEIN, HUMAN; CARBANILAMIDE DERIVATIVE; LY3009120; PYRIMIDINE DERIVATIVE; RAF PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CANCER INHIBITION; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG HALF LIFE; FEMALE; IC50; NONHUMAN; RAT; TUMOR CELL; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOAVAILABILITY; CHEMISTRY; DOG; DRUG EFFECTS; DRUG SCREENING; GENETICS; HALF LIFE TIME; HUMAN; MALE; METABOLISM; MOLECULARLY TARGETED THERAPY; MUTATION; NUDE MOUSE; SPRAGUE DAWLEY RAT; STRUCTURE ACTIVITY RELATION; SYNTHESIS; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; BIOLOGICAL AVAILABILITY; CELL LINE, TUMOR; CHEMISTRY TECHNIQUES, SYNTHETIC; DOGS; FEMALE; HALF-LIFE; HUMANS; MALE; MICE, NUDE; MOLECULAR TARGETED THERAPY; MUTATION; PHENYLUREA COMPOUNDS; PROTO-ONCOGENE PROTEINS B-RAF; PROTO-ONCOGENE PROTEINS C-RAF; PYRIMIDINES; RAS PROTEINS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84930631840     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b00067     Document Type: Article

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