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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
23
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pubmed:dateCreated |
2010-11-8
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pubmed:abstractText |
Herein we report the discovery and synthesis of a novel series of dihydrothieno- and dihydrofuropyrimidines (2 and 3) as potent pan Akt inhibitors. Utilizing previous SAR and analysis of the amino acid sequences in the binding site we have designed inhibitors displaying increased PKA and general kinase selectivity with improved tolerability compared to the progenitor pyrrolopyrimidine (1). A representative dihydrothieno compound (34) was advanced into a PC3-NCI prostate mouse tumor model in which it demonstrated a dose-dependent reduction in tumor growth and stasis when dosed orally daily at 200 mg/kg.
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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 |
Dec
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:BencsikJosef RJR,
pubmed-author:BlakeJames FJF,
pubmed-author:BrandhuberBarbara JBJ,
pubmed-author:DizonFaithF,
pubmed-author:GloorSusan LSL,
pubmed-author:KallanNicholas CNC,
pubmed-author:MartinsonMatthewM,
pubmed-author:MitchellIan SIS,
pubmed-author:MurrayLesley JLJ,
pubmed-author:PriorWei WeiWW,
pubmed-author:RisomTylerT,
pubmed-author:SkeltonNicholas JNJ,
pubmed-author:SpencerKeith LKL,
pubmed-author:TotBB,
pubmed-author:VigersGuy P AGP,
pubmed-author:WoessnerRichard DRD,
pubmed-author:WuWen-IWI,
pubmed-author:XiaoDengmingD
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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 |
7037-41
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pubmed:meshHeading |
pubmed-meshheading:20971641-Animals,
pubmed-meshheading:20971641-Binding Sites,
pubmed-meshheading:20971641-Disease Models, Animal,
pubmed-meshheading:20971641-Dose-Response Relationship, Drug,
pubmed-meshheading:20971641-Male,
pubmed-meshheading:20971641-Mice,
pubmed-meshheading:20971641-Prostatic Neoplasms,
pubmed-meshheading:20971641-Protein Kinase Inhibitors,
pubmed-meshheading:20971641-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:20971641-Pyrimidines,
pubmed-meshheading:20971641-Structure-Activity Relationship,
pubmed-meshheading:20971641-Tumor Burden
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pubmed:year |
2010
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pubmed:articleTitle |
Discovery of dihydrothieno- and dihydrofuropyrimidines as potent pan Akt inhibitors.
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pubmed:affiliation |
Array BioPharma Inc., Boulder, CO 80301, USA. jbencsik@arraybiopharma.com
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pubmed:publicationType |
Journal Article
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