Li Zhong-Rui, Gu Meng-Zhen, Xu Xiao, Zhang Jing-Han, Zhang Hai-Li, Han Chao
Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China; State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Chin J Nat Med. 2022 Apr;20(4):241-257. doi: 10.1016/S1875-5364(22)60141-9.
Lysine specific demethylase 1 (LSD1), a transcriptional corepressor or coactivator that serves as a demethylase of histone 3 lysine 4 and 9, has become a potential therapeutic target for cancer therapy. LSD1 mediates many cellular signaling pathways and regulates cancer cell proliferation, invasion, migration, and differentiation. Recent research has focused on the exploration of its pharmacological inhibitors. Natural products are a major source of compounds with abundant scaffold diversity and structural complexity, which have made a major contribution to drug discovery, particularly anticancer agents. In this review, we briefly highlight recent advances in natural LSD1 inhibitors over the past decade. We present a comprehensive review on their discovery and identification process, natural plant sources, chemical structures, anticancer effects, and structure-activity relationships, and finally provide our perspective on the development of novel natural LSD1 inhibitors for cancer therapy.
赖氨酸特异性去甲基化酶1（LSD1）是一种转录共抑制因子或共激活因子，作为组蛋白3赖氨酸4和9的去甲基化酶，已成为癌症治疗的潜在靶点。LSD1介导许多细胞信号通路，调节癌细胞的增殖、侵袭、迁移和分化。最近的研究集中在探索其药理学抑制剂。天然产物是具有丰富骨架多样性和结构复杂性的化合物的主要来源，这为药物发现，尤其是抗癌药物的发现做出了重大贡献。在这篇综述中，我们简要强调了过去十年中天然LSD1抑制剂的最新进展。我们对它们的发现和鉴定过程、天然植物来源、化学结构、抗癌作用以及构效关系进行了全面综述，最后对用于癌症治疗的新型天然LSD1抑制剂的开发提出了我们的观点。
