Abstract
Non-ATP competitive pyrimidine-based inhibitors of CaMKIIdelta were identified. Computational studies were enlisted to predict the probable mode of binding. The results of the computational studies led to the design of ATP competitive inhibitors with optimized hinge interactions. Inhibitors of this class possessed improved enzyme and cellular activity compared to early leads.
MeSH terms
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Adenosine Triphosphate / metabolism
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Binding, Competitive
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / antagonists & inhibitors*
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Drug Design*
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology*
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Models, Chemical
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Pyrimidines / chemistry
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Pyrimidines / pharmacology*
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Structure-Activity Relationship
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Substrate Specificity
Substances
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Enzyme Inhibitors
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Pyrimidines
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Adenosine Triphosphate
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CAMK2D protein, human
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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pyrimidine