Aryl–indolyl maleimides as inhibitors of CaMKIIδ. Part 3: Importance of the indole orientation

A family of aryl-substituted maleimides was prepared and studied for their activity against calmodulin dependant kinase. Inhibitory activities against the enzyme ranged from 10 nM to >20 μM 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.

Graphical abstractAryl-substituted maleimides were prepared and studied for their activity against CaMKII. Inhibitory activities ranged from 10 nM to >20 μM. Key predicted interactions with the kinase ATP site and hinge region were confirmed.Figure optionsDownload full-size imageDownload as PowerPoint slide