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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
20
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pubmed:dateCreated |
2009-10-15
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pubmed:abstractText |
The discovery and optimization of a novel series of aminoisoquinolines as potent, selective, and efficacious inhibitors of the mutant B-Raf pathway is presented. The N-linked pyridylpyrimidine benzamide 2 was identified as a potent, modestly selective inhibitor of the B-Raf enzyme. Replacement of the benzamide with an aminoisoquinoline core significantly improved kinase selectivity and imparted favorable pharmacokinetic properties, leading to the identification of 1 as a potent antitumor agent in xenograft models.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:BabijCarolC,
pubmed-author:BeltranPedroP,
pubmed-author:CarnahanJosetteJ,
pubmed-author:DeMorinFrenel FFF,
pubmed-author:DohertyElizabeth MEM,
pubmed-author:EpsteinLinda FLF,
pubmed-author:FernandoManoryM,
pubmed-author:HessKristenK,
pubmed-author:HuangQiQ,
pubmed-author:KimJoseph LJL,
pubmed-author:LeQuynhQ,
pubmed-author:LeeMatthew RMR,
pubmed-author:NixeyThomasT,
pubmed-author:ParasNick ANA,
pubmed-author:PetkusJeffrey KJK,
pubmed-author:RoseMark JMJ,
pubmed-author:SmithAdrian LAL,
pubmed-author:WhittingtonDouglas ADA
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pubmed:issnType |
Electronic
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pubmed:day |
22
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pubmed:volume |
52
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6189-92
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pubmed:meshHeading |
pubmed-meshheading:19764794-Administration, Oral,
pubmed-meshheading:19764794-Animals,
pubmed-meshheading:19764794-Biological Availability,
pubmed-meshheading:19764794-Cell Line, Tumor,
pubmed-meshheading:19764794-Drug Discovery,
pubmed-meshheading:19764794-Humans,
pubmed-meshheading:19764794-Isoquinolines,
pubmed-meshheading:19764794-MAP Kinase Signaling System,
pubmed-meshheading:19764794-Male,
pubmed-meshheading:19764794-Mice,
pubmed-meshheading:19764794-Models, Molecular,
pubmed-meshheading:19764794-Molecular Conformation,
pubmed-meshheading:19764794-Mutant Proteins,
pubmed-meshheading:19764794-Mutation,
pubmed-meshheading:19764794-Protein Kinase Inhibitors,
pubmed-meshheading:19764794-Proto-Oncogene Proteins B-raf,
pubmed-meshheading:19764794-Rats,
pubmed-meshheading:19764794-Substrate Specificity
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pubmed:year |
2009
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pubmed:articleTitle |
Selective inhibitors of the mutant B-Raf pathway: discovery of a potent and orally bioavailable aminoisoquinoline.
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pubmed:affiliation |
Department of Medicinal Chemistry, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320-1799, USA. adrians@amgen.com
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pubmed:publicationType |
Journal Article
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