组蛋白去甲基化酶LSD1抑制剂临床研究进展  

Advances on clinical research of histone demethylase LSD1 inhibitors

作　　者：史宇婷 杨欣语 余斌[1] 宋宜辉 SHI Yu-ting;YANG Xin-yu;YU Bin;SONG Yi-hui(School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001,China)

机构地区：[1]郑州大学药学院,河南郑州450001

出　　处：《药学学报》2022年第10期2949-2959,I0004,共12页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(31900875,81973177);河南省自然科学基金优秀青年基金项目(222300420069);河南省高校科技创新人才支持计划(21HASTIT045)。

摘　　要：赖氨酸特异性去甲基化酶1(lysine-specific demethylase 1,LSD1)在细胞干性、分化、细胞运动、代谢控制和上皮-间充质转化等过程中发挥着重要作用,与肿瘤的增殖、侵袭转移和不良预后等过程密切相关,同时也是其他疾病如神经退行性疾病和病毒感染等的潜在治疗靶标。自2013年开始,不可逆抑制剂tranylcypromine、ORY-1001、ORY-2001、GSK-2879552、IMG-7289、INCB059872、TAK-418、LH-1802及可逆抑制剂CC-90011和SP-2577先后获批开展临床试验。本综述全面阐述了LSD1候选药物的临床研究现状,并对LSD1靶向药物研发的前景、存在的机遇与挑战进行了概述,旨在为相关药物研发提供参考。Lysine-specific demethylase 1(LSD1)plays vital roles in cell stemness,differentiation,cell motility,metabolic control and epithelial-mesenchymal transition,which is closely associated with tumorigenesis processes including cell proliferation,invasive,metastasis and poor prognosis.Besides,LSD1 also contributes to the occurrence of other diseases such as neurodegenerative diseases and viral infections.Since 2013,the irreversible inhibitors including tranylcypromine,ORY-1001,ORY-2001,GSK-2879552,IMG-7289,INCB059872,TAK-418,LH-1802 and reversible inhibitors including CC-90011 and SP-2577 have been approved for clinical assessment.This review comprehensively summarizes the clinical research of LSD1 drug candidates and briefly discusses the prospects,opportunities and challenges of LSD1-targeted drug discovery,aiming to provide a landscape for the related drug development.

关 键 词：表观遗传 组蛋白去甲基化酶 赖氨酸特异性去甲基化酶1抑制剂 临床试验 药物研发 

分 类 号：R914[医药卫生—药物化学]