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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2010-4-5
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pubmed:abstractText |
A series of benzofuran-3-one indole phosphatidylinositol-3-kinases (PI3K) inhibitors identified via HTS has been prepared. The optimized inhibitors possess single digit nanomolar activity against p110alpha (PI3K-alpha), good pharmaceutical properties, selectivity versus p110gamma (PI3K-gamma), and tunable selectivity versus the mammalian target of rapamycin (mTOR). Modeling of compounds 9 and 32 in homology models of PI3K-alpha and mTOR supports the proposed rationale for selectivity. Compounds show activity in multiple cellular proliferation assays with signaling through the PI3K pathway confirmed via phospho-Akt inhibition in PC-3 cells.
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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 |
Apr
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pubmed:issn |
1464-3405
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pubmed:author |
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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 |
15
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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 |
2586-90
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:20303263-Benzofurans,
pubmed-meshheading:20303263-Cell Line, Tumor,
pubmed-meshheading:20303263-Humans,
pubmed-meshheading:20303263-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:20303263-Models, Molecular,
pubmed-meshheading:20303263-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:20303263-Protein Kinase Inhibitors,
pubmed-meshheading:20303263-Protein-Serine-Threonine Kinases,
pubmed-meshheading:20303263-Structure-Activity Relationship,
pubmed-meshheading:20303263-TOR Serine-Threonine Kinases
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pubmed:year |
2010
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pubmed:articleTitle |
Novel benzofuran-3-one indole inhibitors of PI3 kinase-alpha and the mammalian target of rapamycin: hit to lead studies.
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pubmed:affiliation |
Medicinal Chemistry, Chemical Sciences, Wyeth Research, Pearl River, NY 10965, USA.
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pubmed:publicationType |
Journal Article
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