Histone demethylase inhibitors: developmental insights and current status

Abstract

The discovery of histone demethylases (HDMs) has greatly advanced our epigenetic understanding, particularly their role in post-translational modifications of histones. HDMs regulate cellular functions, such as X chromosome inactivation, differentiation, cell-based aging, and deoxyribonucleic acid (DNA) damage repair. Although crucial for regulating genetic expression, post-translational modifications have been implicated in developing several diseases. The discovery and development of inhibitors targeting HDMs have emerged as an active and rapidly expanding research field over the last few years. This review attempts to collate the available information on different isoforms of HDMs, substrate selectivity, and involvement in various biological functions. Also, the existing as well as emerging HDM inhibitors, especially inhibitors of histone lysine (K) demethylase 1 (KDM1) and the jumonji-C (JmjC) family demethylases (KDM 2–8), are reported along with analysis on insights for the future development of HDM inhibitors.