Design strategies for protein kinase inhibitors

Deregulation of protein kinases due to mutation or overexpression is a hallmark of several diseases, for example, cancer, diabetes, inflammation and cardiovascular disorders. Consequently, there has been a growing interest in the discovery of protein kinase inhibitors as novel drugs. Here, we focus on key milestones and advances in protein kinase inhibitor drug discovery over the last year, with an emphasis on novel strategies such as targeting of single and multiple binding sites, inactive conformations of kinases, allosteric sites, regulatory domains and heat shock proteins. We will highlight recent developments for specific inhibitors in clinical studies for growth factor receptors, non-receptor tyrosine kinases and serine/threonine kinases.