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.
Structural Genomics Consortium, University of Toronto, 101 College St., Toronto, ON M5G 1L7, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: matthieu.schapira@utoronto.ca.
Matthieu
M
Schapira
Structural Genomics Consortium, University of Toronto, 101 College St., Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, 101 College St., Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Centre, 101 College St., Toronto, ON M5G 1L7, Canada. Electronic address: carrow@uhnres.utoronto.ca.
Cheryl H
CH
Arrowsmith
D004791:Enzyme Inhibitors / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D006801:Humans; D008780:Methyltransferases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D008780:Methyltransferases