Selective inhibitors of the mutant B-Raf pathway: Discovery of a potent and orally bioavailable aminoisoquinoline

Journal of Medicinal Chemistry

Volumn 52, Issue 20, 2009, Pages 6189-6192

  Smith, Adrian L ^a   DeMorin, Frenel F ^a   Paras, Nick A ^a   Huang, Qi ^a   Petkus, Jeffrey K ^a   Doherty, Elizabeth M ^a   Nixey, Thomas ^a   Kim, Joseph L ^a   Whittington, Douglas A ^a   Epstein, Linda F ^a   Lee, Matthew R ^a   Rose, Mark J ^a   Babij, Carol ^a   Fernando, Manory ^a   Hess, Kristen ^a   Le, Quynh ^a   Beltran, Pedro ^a   Carnahan, Josette ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOISOQUINOLINE; ANTINEOPLASTIC AGENT; B RAF KINASE; ISOQUINOLINE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CRYSTAL STRUCTURE; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG IDENTIFICATION; DRUG SCREENING; DRUG STRUCTURE; ENZYME PHOSPHORYLATION; HUMAN; IN VIVO STUDY; NONHUMAN; XENOGRAFT;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; CELL LINE, TUMOR; DRUG DISCOVERY; HUMANS; ISOQUINOLINES; MALE; MAP KINASE SIGNALING SYSTEM; MICE; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MUTANT PROTEINS; MUTATION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS B-RAF; RATS; SUBSTRATE SPECIFICITY;

EID: 70350061746     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm901081g     Document Type: Article

References (24)

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22. The cocrystal structure of B-Raf with 1 has been deposited in the Protein Data Bank with accession code 3IDP.
23. Human A375 cells were selected in vivo by passaging twice subcutaneously in CD1 nu/nu mice to optimize for tumor take and growth. This cell line was designated A375 SQ2.
24. Compound was dosed QD in a randomized, blinded experiment for 14 days starting 17 days postimplantation.