Abstract
Crystallographic and modelling data, in conjunction with a medicinal chemistry template-hopping approach, led to the identification of a series of novel and potent inhibitors of human cyclin-dependent kinase 2 (CDK2), with selectivity over glycogen synthase kinase-3beta (GSK-3beta). One example had a CDK2 IC(50) of 120 nM and showed selectivity over GSK-3beta of 167-fold.
MeSH terms
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Cell Line, Tumor
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Cyclin-Dependent Kinase 2 / antagonists & inhibitors*
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Cyclin-Dependent Kinase 2 / metabolism
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Drug Design*
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Humans
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Inhibitory Concentration 50
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Molecular Structure
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry*
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Pyrimidines / pharmacology*
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Structure-Activity Relationship
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Triazoles / chemistry*
Substances
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Protein Kinase Inhibitors
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Pyrimidines
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Triazoles
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Cyclin-Dependent Kinase 2