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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2010-2-22
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pubmed:abstractText |
Through a combination of screening and structure-based rational design, we have discovered a series of N(1)-(5-(heterocyclyl)-thiazol-2-yl)-3-(4-trifluoromethylphenyl)-1,2-propanediamines that were developed into potent ATP competitive inhibitors of AKT. Studies of linker strand-binding adenine isosteres identified SAR trends in potency and selectivity that were consistent with binding interactions observed in structures of the inhibitors bound to AKT1 and to the counter-screening target PKA. One compound was shown to have acceptable pharmacokinetic properties and to be a potent inhibitor of AKT signaling and of in vivo xenograft tumor growth in a preclinical model of glioblastoma.
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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 |
Mar
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:AllenJohn GJG,
pubmed-author:BourbeauMatthew PMP,
pubmed-author:DominguezCeliaC,
pubmed-author:EschJ FJF,
pubmed-author:FotschChristopherC,
pubmed-author:FreemanDaniel JDJ,
pubmed-author:HoffmanDouglasD,
pubmed-author:HongFang-TsaoFT,
pubmed-author:HuangXinX,
pubmed-author:HungateRandallR,
pubmed-author:LeeMatthew RMR,
pubmed-author:LofgrenJulie AJA,
pubmed-author:RiderJames TJT,
pubmed-author:TadesseSeifuS,
pubmed-author:TomineyElizabethE,
pubmed-author:WangXianghongX,
pubmed-author:YamaneHarvey KHK,
pubmed-author:YangSuijinS,
pubmed-author:YaoGuominG,
pubmed-author:YuanChester CCC,
pubmed-author:ZengQingpingQ,
pubmed-author:ZhangShiwenS,
pubmed-author:ZhangXiaolingX
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pubmed:copyrightInfo |
Copyright 2010 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1559-64
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pubmed:meshHeading |
pubmed-meshheading:20137943-Animals,
pubmed-meshheading:20137943-Antineoplastic Agents,
pubmed-meshheading:20137943-Azoles,
pubmed-meshheading:20137943-Binding Sites,
pubmed-meshheading:20137943-Crystallography, X-Ray,
pubmed-meshheading:20137943-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:20137943-Cyclin-Dependent Kinase 2,
pubmed-meshheading:20137943-Drug Design,
pubmed-meshheading:20137943-Mice,
pubmed-meshheading:20137943-Mice, Nude,
pubmed-meshheading:20137943-Neoplasms,
pubmed-meshheading:20137943-Protein Kinase Inhibitors,
pubmed-meshheading:20137943-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:20137943-Rats,
pubmed-meshheading:20137943-Rats, Sprague-Dawley,
pubmed-meshheading:20137943-Structure-Activity Relationship,
pubmed-meshheading:20137943-Xenograft Model Antitumor Assays
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pubmed:year |
2010
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pubmed:articleTitle |
Azole-based inhibitors of AKT/PKB for the treatment of cancer.
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pubmed:affiliation |
Chemistry Research and Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States.
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pubmed:publicationType |
Journal Article
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