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.
J Med Chem. 2021 Mar 11;64(5):2466-2488. doi: 10.1021/acs.jmedchem.0c02176. Epub 2021 Feb 23.
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.
作为黄素腺嘌呤二核苷酸（FAD）依赖性单胺氧化酶，赖氨酸特异性去甲基化酶 1（LSD1/KDM1A）作为转录共激活因子或共抑制因子发挥作用，调节组蛋白 3 赖氨酸 4 和 9（H3K4/9）的甲基化，并且已成为癌症治疗有前途的表观遗传靶标。迄今为止，已经开发了许多针对 LSD1 的抑制剂，其中一些正在进行癌症治疗的临床试验。尽管只有两种可逆 LSD1 抑制剂 CC-90011 和 SP-2577 处于临床阶段，但在过去十年中，可逆 LSD1 抑制剂的开发取得了显著进展。在此，我们对可逆 LSD1 抑制剂的结构、生物学评价和构效关系（SAR）进行了全面综述。
