赖氨酸特异性去甲基酶1反苯环丙胺类不可逆抑制剂的研究进展

Advances in Research on Tranylcyprominebased Covalent Inhibitors of Lysine-Specific Demethylase 1

摘要: 组蛋白赖氨酸特异性去甲基酶1（LSD1）在调节组蛋白H3K4、H3K9的甲基化状态中起重要作用，在多种肿瘤细胞中高表达，已成为一种新型抗肿瘤靶点。目前为止，已报道的LSD1抑制剂中对反苯环丙胺（TCP）类抑制剂的研究相对更为深入。综述TCP类抑制剂的作用机制、与辅酶黄素腺嘌呤二核苷酸（FAD）结合模式及设计优化的研究进展。

Abstract: Histone lysine-specific demethylase 1 (LSD1), which is highly expressed in various tumor cells, plays an important role in functionally regulating methylation degrees of H3K4 and H3K9. Therefore, it has already been known as a new anti-tumor target. Up to now, deeper researches have been focused on tranylcypromine (TCP)-based inhibitors in all kinds of LSD1 inhibitors. This review aims at TCP's mechanism of inhibition, the modes of combination with coenzyme flavin adenine dinucleotide (FAD) and optimization of its design.