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.

天然产物通常属于与生物相​​关的化学空间，并且始终具有新颖的生物活性，从而使其成为新药发现的先导化合物的丰富来源。随着最新技术的进步，基于天然产物的药物发现现已进入一个新时代。天然产物在表观遗传药物发现方面也显示出前景，其中一些已进入临床试验或目前正在临床使用。组蛋白赖氨酸特异性去甲基化酶 1 (LSD1) 是一类重要的组蛋白去甲基化酶，在各种病理状况的发展中具有重要作用。靶向 LSD1 已被认为是癌症治疗的一种有前途的治疗选择。值得注意的是，一些具有不同化学型的天然产物，包括原小檗碱生物碱、黄酮、多酚和环肽，已显示出对抗 LSD1 的有效性。这些天然产物为开发新的 LSD1 抑制剂提供了新的支架。本文主要讨论天然LSD1抑制剂的鉴定、LSD1/天然产物复合物的共晶结构分析、抗肿瘤活性及其作用方式。我们还简要讨论了该领域面临的挑战。我们相信这篇综述将提供天然 LSD1 抑制剂的概况。