Yuan Fang, Chao Yang, Zhiqiang Yu, Xiaochuan Li, Qingchun Mu, Guochao Liao, Bin Yu. Natural products as LSD1 inhibitors for cancer therapy[J]. Acta Pharmaceutica Sinica B, 2021, 11(3): 621-631

Natural products as LSD1 inhibitors for cancer therapy
Yuan Fangb, Chao Yangd, Zhiqiang Yue, Xiaochuan Lic, Qingchun Muc, Guochao Liaob, Bin Yua,f
a School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China;
b Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China;
c The People's Hospital of Gaozhou, Gaozhou 525200, China;
d Institute of Innovation & Application, Zhejiang Ocean University, Zhoushan 316022, China;
e School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China;
f State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
Natural products generally fall into the biologically relevant chemical space and always possess novel biological activities, thus making them a rich source of lead compounds for new drug discovery. With the recent technological advances, natural product-based drug discovery is now reaching a new era. Natural products have also shown promise in epigenetic drug discovery, some of them have advanced into clinical trials or are presently being used in clinic. The histone lysine specific demethylase 1 (LSD1), an important class of histone demethylases, has fundamental roles in the development of various pathological conditions. Targeting LSD1 has been recognized as a promising therapeutic option for cancer treatment. Notably, some natural products with different chemotypes including protoberberine alkaloids, flavones, polyphenols, and cyclic peptides have shown effectiveness against LSD1. These natural products provide novel scaffolds for developing new LSD1 inhibitors. In this review, we mainly discuss the identification of natural LSD1 inhibitors, analysis of the co-crystal structures of LSD1/natural product complex, antitumor activity and their modes of action. We also briefly discuss the challenges faced in this field. We believe this review will provide a landscape of natural LSD1 inhibitors.
Key words:    Epigenetic regulation    Histone demethylase    Natural products    LSD1 inhibitors    Drug discovery    Cancer therapy   
Received: 2020-04-28     Revised: 2020-05-30
DOI: 10.1016/j.apsb.2020.06.007
Funds: We are grateful for the financial support from the National Natural Science Foundation of China (Nos. 81703326, 81973177, 81773580 and 81802130), China Postdoctoral Science Foundation (Nos. 2018M630840 and 2019T120641), the Open Project of State Key Laboratory of Natural Medicines (No. SKLNMKF202005, China), and Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine (No. 2018B030322011, China).
Corresponding author: Qingchun Mu, Guochao Liao, Bin Yu;;
Author description:
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Yuan Fang
Chao Yang
Zhiqiang Yu
Xiaochuan Li
Qingchun Mu
Guochao Liao
Bin Yu

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