Recent Advances in Small-Molecule Modulation of Epigenetic Targets

The last few years have seen significant progress in the development of small-molecule inhibitors of epigenetic targets for cancer. In particular, the most advanced programs have been focused on two target classes: histone methyltransferases (HMTs) and bromodomains. They represent a subset of the many enzymes and proteins that modify histone lysines and that recognize those modifications. In this account are highlighted the discovery and development of G9a, EZH2, DOT1L, and BET inhibitors. Examples of both HMT and bromodomain inhibitors are currently being evaluated in human clinical trials for various therapeutic applications in oncology and cardiovascular disease.