Degraders of histone lysine methyltransferases: Progress, challenges, and opportunities
Mengling Yang1, Qiangsheng Zhang1, Jing Yang1
1School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China.
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.
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