Reversible Lysine Specific Demethylase 1 (LSD1) Inhibitors: A Promising Wrench to Impair LSD1

  • J Med Chem. 2021 Mar 11;64(5):2466-2488. doi: 10.1021/acs.jmedchem.0c02176.
Xing-Jie Dai  1 ,  Ying Liu  1 ,  Lei-Peng Xue  1 ,  Xiao-Peng Xiong  1 ,  Ying Zhou  1 ,  Yi-Chao Zheng  1 ,  Hong-Min Liu  1
Affiliations
  • 1. Key Lab of Advanced Drug Preparation Technologies, Ministry of Education of China, State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Henan Province for Drug Quality and Evaluation, Institute of Drug Discovery and Development, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.
PMID: 33619958 DOI: 10.1021/acs.jmedchem.0c02176
Abstract

As a flavin adenine dinucleotide (FAD)-dependent Monoamine Oxidase, lysine specific demethylase 1 (LSD1/KDM1A) functions as a transcription coactivator or corepressor to regulate the methylation of histone 3 lysine 4 and 9 (H3K4/9), and it has emerged as a promising epigenetic target for Anticancer treatment. To date, numerous inhibitors targeting LSD1 have been developed, some of which are undergoing clinical trials for Cancer therapy. Although only two reversible LSD1 inhibitors CC-90011 and SP-2577 are in the clinical stage, the past decade has seen remarkable advances in the development of reversible LSD1 inhibitors. Herein, we provide a comprehensive review about structures, biological evaluation, and structure-activity relationship (SAR) of reversible LSD1 inhibitors.

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