Novel Drugs Targeting the Epigenome

Epigenetic drug discovery has its beginning in the cancer research arena, focusing first on DNA methylation and histone deacetylation. There are currently two DNA methyltransferase (DNMT) inhibitors and four histone deacetylase (HDAC) inhibitors approved by the US Food and Drug Administration (FDA) during the past 13 years. Over the past few years, breakthrough discoveries of chromatin-modifying enzymes and associated mechanisms have exploded, providing new insights into the role of epigenetic control in gene regulation and leading to the discovery of a variety of new and specific drug targets. Among them, epigenetic “reader”—bromodomain and extra-terminal protein (BET), “writers”—disruptor of telomeric silencing 1-like (DOT1L), enhancer of zeste homolog 2 (EZH2), and protein arginine methyltransferase 5 (PRMT5), and “erasers”—lysine-specific histone demethylase 1 (LSD1) as well as isocitrate dehydrogenase (IDH) attract greater attention due to the ongoing clinical trials. This article provides a brief overview of new drugs modulating the above epigenetic targets, including their indication, mechanism of action, and disclosed chemical structures. The trend of epigenetic drug approval in the following few years is expectable, at least partially, from current clinical trials summarized in this review.