Recent progress in developing selective inhibitors of protein methyltransferases

Mounting evidence suggests that protein methyltransferases (PMTs), which catalyze methylation of histones as well as non-histone proteins, play a crucial role in diverse biological pathways and human diseases. In particular, PMTs have been recognized as major players in regulating gene expression and chromatin state. There has been an increasingly growing interest in these enzymes as potential therapeutic targets and over the past two years tremendous progress has been made in the discovery of selective, small molecule inhibitors of protein lysine and arginine methyltransferases. Inhibitors of PMTs have been used extensively in oncology studies as tool compounds, and inhibitors of EZH2, DOT1L and PRMT5 are currently in clinical trials.