Recent advances in irreversible kinase inhibitors.

Despite concerns of off-target selectivity and cytotoxicity, there has been a resurgence in interest in irreversible kinase inhibitors resulting in more than 60 disclosed patent and patent applications over the past 4 years. Many of these inhibitors possess several key advantages over their reversible counterparts. The patent literature from 2010 to 2013 has been reviewed and novel irreversible kinase inhibitors for Bruton's tyrosine kinase, epidermal growth factor receptor, Janus kinase 3, phosphoinsitide 3 and other kinases are disclosed and discussed. These inhibitors offer novel treatments for mantle cell lymphoma, non-small-cell lung cancer, autoimmune disorders and severe metastatic cancers. A future perspective is presented on the likelihood of clinical success of these agents as well as the potential for new uses of irreversible kinase inhibitors in the future.