Future strategies in epigenetic drug discovery

Most current research aimed at the discovery of epigenetic therapies adheres to the paradigm of target-based drug discovery, focusing on the modulation of single enzymes involved in DNA methylation and histone modifications. The recent discovery of promising small molecule inhibitors for a class of nonenzymatic chromatin regulators, the BET bromodomains, suggests that future drug discovery for epigenetic therapy will involve the modulation of protein–protein interactions and multiprotein complexes. Also, it is expected that target-based discovery strategies will be increasingly complemented by approaches based on chemical probes generated by phenotypic or mechanistic cell-based screening.