Methyltransferase inhibitors for modulation of the epigenome and beyond

Over the past two years tremendous progress has been made in the discovery of new inhibitors of protein lysine and arginine methyltransferases, establishing this class of epigenetic enzymes, along with DNA methyltransferases, as druggable protein families. New inhibitors of protein methyltransferases have been described with a variety of mechanisms of action including cofactor competitive, substrate competitive, allosteric inhibitors and disruptors of protein-protein interactions. Inhibitors have been used extensively in oncology studies, and inhibitors of EZH2, and DOT1L are currently in clinical trials. Finally, advances in understanding the clinical mechanism of action of 5-azacytidine and related DNA hypomethylation agents were reported, revealing a likely role for a cell autonomous innate immune response.