Drug discovery of histone lysine demethylases (KDMs) inhibitors (progress from 2018 to present)

Post-translational modifications (PTMs) of histone by histone demethylases (KDMs) play an important role in the regulation of gene expression, which implicates the development of various human cancers and other diseases. Discovering and developing inhibitors targeting KDMs have become an active and fast-growing research area over the past decades. In this review, the latest emerging small-molecule inhibitors of KDMs were surveyed with the emphasis on the literature since 2018, including lysine specific demethylases (LSD or KDM1) inhibitors and JmjC family N-methyl lysine demethylases (JmjC KDMs, i.e. KDM2-7) inhibitors. The drug design strategy, the structure-activity relationships (SARs), the analysis and insight of co-crystal structures, and the mechanisms of action (MOA) were also discussed.(c) 2022 Elsevier Masson SAS. All rights reserved.

Automated summary

Post-translational modifications (PTMs) of histone by histone demethylases (KDMs) are important for gene expression regulation and are implicated in the development of various human cancers and diseases. This review surveys the latest small-molecule inhibitors of KDMs, focusing on literature since 2018, including inhibitors of lysine-specific demethylases (LSD or KDM1) and JmjC family N-methyl lysine demethylases (JmjC KDMs, i.e. KDM2-7). The review also discusses drug design strategy, structure-activity relationships (SARs), analysis of co-crystal structures, and mechanisms of action (MOA).