Abstract
A family of aryl-substituted maleimides was prepared and studied for their activity against calmodulin dependant kinase. Inhibitory activities against the enzyme ranged from 10nM to >20microM and were dependant upon both the nature of the aryl group and the tether joining the basic amine to the indolyl maleimide core of the inhibitors. Key interactions with the kinase ATP site and hinge region, predicted by homology modeling, were confirmed.
MeSH terms
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Adenosine Triphosphate / metabolism
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Benzene Derivatives / chemical synthesis
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Benzene Derivatives / pharmacology*
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Binding Sites
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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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Hydrophobic and Hydrophilic Interactions
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Indoles / chemical synthesis
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Indoles / pharmacology*
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Maleimides / chemical synthesis
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Maleimides / pharmacology*
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Models, Chemical
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Structure-Activity Relationship
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Substrate Specificity
Substances
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Benzene Derivatives
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Enzyme Inhibitors
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Indoles
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Maleimides
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Adenosine Triphosphate
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CAMK2D protein, human
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Calcium-Calmodulin-Dependent Protein Kinase Type 2