Degraders of histone lysine methyltransferases: Progress, challenges, and opportunities.

Authors

Mengling Yang, Qiangsheng Zhang, Jing Yang, Ruini Cheng, Xianli Zhou

Published in

Drug discovery today. Pages 104756. Aug 01, 2026. Epub Aug 01, 2026.

Abstract

Histone lysine methyltransferases (HKMTs) are a class of enzymes capable of catalyzing the methylation modification of lysine residues on histones. Members of the lysine methyltransferase family, such as EZH2, G9a, DOT1L, NSD2, NSD3, and ASH1L, show overexpression, abnormal activation, or mutations in various diseases. HKMT inhibitors are under intense development, but most have drawbacks such as poor efficacy. Targeted protein degraders (TPDs) offer the benefit of controlling both the enzymatic and non-enzymatic activities of the target protein, serving as a method to offset the limitations of inhibitors. This manuscript presents 31 degraders targeting six lysine methyltransferases, offering insights into their development potential and serving as a valuable reference for pharmacologists and researchers.

PMID:
42542162
Bibliographic data and abstract were imported from PubMed on 02 Aug 2026.

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