LSD1 in drug discovery: From biological function to clinical application

• Published in: Medicinal research reviews Vol. 44; no. 2; pp. 833 - 866
• Main Authors: Liu, Hui‐Min, Zhou, Ying, Chen, He‐Xiang, Wu, Jiang‐Wan, Ji, Shi‐Kun, Shen, Liang, Wang, Shao‐Peng, Liu, Hong‐Min, Liu, Ying, Dai, Xing‐Jie, Zheng, Yi‐Chao
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2024
• Subjects: Ablation; Biological activity; Cancer; clinical trial; Clinical trials; Drug Discovery; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Histone Demethylases - metabolism; Histone Demethylases - therapeutic use; Histones; Humans; inhibitor; LSD1; Lysine - therapeutic use; Monoamine Oxidase Inhibitors - therapeutic use; Neoplasms - drug therapy; R&D; Research & development; clinical trial; biological activity; inhibitor; LSD1
• ISSN: 0198-6325; 1098-1128; 1098-1128
• DOI: 10.1002/med.22000

Lysine‐specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono‐, and dimethylation of histone 3 lysine 4 (H3K4), resulting in the suppression of target gene transcriptions. Besides, it can also demethylate some nonhistone substrates to regulate their biological functions. As reported, LSD1 is widely upregulated and plays a key role in several kinds of cancers, pharmacological or genetic ablation of LSD1 in cancer cells suppresses cell aggressiveness by several distinct mechanisms. Therefore, numerous LSD1 inhibitors, including covalent and noncovalent, have been developed and several of them have entered clinical trials. Herein, we systemically reviewed and discussed the biological function of LSD1 in tumors, lymphocytes as well as LSD1‐targeting inhibitors in clinical trials, hoping to benefit the field of LSD1 and its inhibitors.