Synthesis and isozyme selectivity of small molecule protein kinase C inhibitors: a review of patents

Protein kinase C (PKC) is a ubiquitously expressed family of kinases that have key roles in the transduction of signals mediated by the hydrolysis of phospholipids for cell proliferation, gene expression, migration, differentiation and a host of other functions. Each of the 12 isozymes of PKC govern both the positive and negative aspects of cell signalling with opposing effects at times. The roles of different PKC isozymes in various disease conditions is being elucidated and evaluated by researchers at present. The need has emerged for the development of PKC isozyme-specific modulators that have therapeutic value and also help in discovering the myriad signalling pathways governed by these isozymes. This review attempts to give a synopsis of the recent developments in the design and synthesis of such small molecule inhibitors covered by patents during the past five years.