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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
2006-6-1
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pubmed:abstractText |
We describe a series of potent and selective oxindole-pyridine-based protein kinase B/Akt inhibitors. The most potent compound 11n in this series demonstrated an IC(50) of 0.17nM against Akt1 and more than 100-fold selectivity over other Akt isozymes. The selectivity against other protein kinases was highly dependent on the C-3 substitutions at the oxindole scaffold, with unsubstituted 9e or 3-furan-2-ylmethylene (11n) more selective and 3-(1H-pyrrol-2-yl)methylene (11f) or 3-(1H-imidazol-2-yl)methylene (11k) less selective. In a mouse xenograft model, 9d, 11f, and 11n inhibited tumor growth but with accompanying toxicity.
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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 |
Jul
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pubmed:issn |
0960-894X
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pubmed:author |
pubmed-author:BouskaJenniferJ,
pubmed-author:ChuI YIY,
pubmed-author:GandhiViraj BVB,
pubmed-author:GirandaVincent LVL,
pubmed-author:GongJianchunJ,
pubmed-author:GuanRanR,
pubmed-author:JarvisKenK,
pubmed-author:JohnsonEric FEF,
pubmed-author:JongRon DeRD,
pubmed-author:KlinghoferVeredV,
pubmed-author:LiQunQ,
pubmed-author:LiuXuesongX,
pubmed-author:LuoYanY,
pubmed-author:MagnoneShayna RSR,
pubmed-author:OleksijewAnatolA,
pubmed-author:OltersdorfTilmanT,
pubmed-author:ParkChangC,
pubmed-author:RosenbergSaul HSH,
pubmed-author:ShoemakerAlexanderA,
pubmed-author:ZhuGui-DongGD
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3424-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16644221-Animals,
pubmed-meshheading:16644221-Antineoplastic Agents,
pubmed-meshheading:16644221-Cell Line, Tumor,
pubmed-meshheading:16644221-Cell Proliferation,
pubmed-meshheading:16644221-Crystallography, X-Ray,
pubmed-meshheading:16644221-Dose-Response Relationship, Drug,
pubmed-meshheading:16644221-Indoles,
pubmed-meshheading:16644221-Mice,
pubmed-meshheading:16644221-Models, Molecular,
pubmed-meshheading:16644221-Molecular Structure,
pubmed-meshheading:16644221-Neoplasms,
pubmed-meshheading:16644221-Protein Kinase Inhibitors,
pubmed-meshheading:16644221-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:16644221-Pyridines,
pubmed-meshheading:16644221-Stereoisomerism,
pubmed-meshheading:16644221-Structure-Activity Relationship,
pubmed-meshheading:16644221-Xenograft Model Antitumor Assays
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pubmed:year |
2006
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pubmed:articleTitle |
Discovery and SAR of oxindole-pyridine-based protein kinase B/Akt inhibitors for treating cancers.
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pubmed:affiliation |
Cancer Research, GPRD, Abbott Laboratories, Abbott Park, IL 60064, USA. gui-dong.zhu@abbott.com
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pubmed:publicationType |
Journal Article
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