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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
25
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pubmed:dateCreated |
2001-11-30
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pubmed:abstractText |
Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepared as a homologue of the 3-benzylidene-1,3-dihydro-2H-indol-2-one class of kinase inhibitor. Crystallographic analysis of the lead compound bound to CDK2 provided the basis for analogue design. A semiautomated method of ligand docking was used to select compounds for synthesis, and a number of compounds with low nanomolar inhibitory activity versus CDK2 were identified. Enzyme binding determinants for several analogues were evaluated by X-ray crystallography. Compounds in this series inhibited CDK2 with a potency approximately 10-fold greater than that for CDK1. Members of this class of inhibitor cause an arrest of the cell cycle and have shown potential utility in the prevention of chemotherapy-induced alopecia.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CDC2-CDC28 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/CDK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrazones,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Isatin,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BramsonH NHN,
pubmed-author:CoronaJJ,
pubmed-author:DavisS TST,
pubmed-author:DickersonS HSH,
pubmed-author:EdelsteinMM,
pubmed-author:FryeS VSV,
pubmed-author:GampeR TRTJr,
pubmed-author:HarrisP APA,
pubmed-author:HassellAA,
pubmed-author:HolmesW DWD,
pubmed-author:HunterR NRN,
pubmed-author:KuyperL FLF,
pubmed-author:LackeyK EKE,
pubmed-author:LovejoyBB,
pubmed-author:LuzzioM JMJ,
pubmed-author:MontaniNN,
pubmed-author:RocqueW JWJ,
pubmed-author:RusnakDD,
pubmed-author:ShewchukLL,
pubmed-author:VealJ MJM,
pubmed-author:WalkerD HDH
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4339-58
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11728181-Antineoplastic Agents,
pubmed-meshheading:11728181-CDC2-CDC28 Kinases,
pubmed-meshheading:11728181-Crystallography, X-Ray,
pubmed-meshheading:11728181-Cyclin-Dependent Kinase 2,
pubmed-meshheading:11728181-Cyclin-Dependent Kinases,
pubmed-meshheading:11728181-Drug Screening Assays, Antitumor,
pubmed-meshheading:11728181-Enzyme Inhibitors,
pubmed-meshheading:11728181-G1 Phase,
pubmed-meshheading:11728181-Humans,
pubmed-meshheading:11728181-Hydrazones,
pubmed-meshheading:11728181-Indoles,
pubmed-meshheading:11728181-Isatin,
pubmed-meshheading:11728181-Models, Molecular,
pubmed-meshheading:11728181-Protein Binding,
pubmed-meshheading:11728181-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11728181-S Phase,
pubmed-meshheading:11728181-Stereoisomerism,
pubmed-meshheading:11728181-Structure-Activity Relationship,
pubmed-meshheading:11728181-Sulfonamides,
pubmed-meshheading:11728181-Tumor Cells, Cultured
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pubmed:year |
2001
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pubmed:articleTitle |
Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis.
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pubmed:affiliation |
GlaxoSmithKline Inc., Five Moore Drive, Research Triangle Park, North Carolina 27709, USA.
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pubmed:publicationType |
Journal Article
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