RNA领域的小分子药物筛选和应用  

Screening and application of small molecule drugs targeting RNA biology

作　　者：陈硕 杨曼 姜海 CHEN Shuo;YANG Man;JIANG Hai(Key Laboratory of RNA Innovation,Science and Engineering,Shanghai Institute of Biochemistry and Cell Biology,Center for Excellence in Molecular Cell Science,Chinese Academy of Sciences,University of Chinese Academy of Sciences,Shanghai 200031,China;Key Laboratory of Systems Health Science of Zhejiang Province,School of Life Science,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou 310024,China)

机构地区：[1]中国科学院分子细胞科学卓越创新中心,上海生物化学与细胞生物学研究所,核糖核酸功能与应用重点实验室,中国科学院大学,上海200031 [2]国科大杭州高等研究院生命与健康科学学院,浙江省系统健康科学重点实验室,中国科学院大学,杭州310024

出　　处：《生命的化学》2024年第9期1728-1736,共9页Chemistry of Life

基　　金：国家重点研发计划项目(2020YFA050022)。

摘　　要：随着对疾病机制的深入研究,RNA的表达、剪切、翻译、稳定性调控等过程已成为疾病干预的新型靶点,为代谢疾病、遗传疾病、肿瘤患者提供了新的治疗模式,并产生了数种创新药物。在RNA药物领域,除了siRNA和反义寡核苷酸,小分子药物也提供了越来越多的成功案例,并且出现了RIBOTAC等新型药物模式。目前,RNA领域的小分子药物已实现了对于RNA的转录、剪切、转运、翻译、稳定性调控等多个生物学过程的靶向调控。本文综述了不同作用机制的RNA领域小分子药物的发展现状,并介绍以RNA为目标的小分子药物的筛选方法。Deepening understanding of disease mechanisms has made RNA biology a promising field for drug development.By intervening with RNA expression,splicing,translation etc,new therapeutic modes have been established for metabolic diseases,inherited diseases and cancer,and several drugs have been approved for patients.In the RNA medicine field,aside from siRNA and antisense oligonucleotide,small molecule has yielded successful drugs,and new modules such as RIBOTAC are also emerging.Existing small molecules can modify many steps of RNA biology,including its transcription,splicing,transport,translation and stability control.In this review,we discuss small molecule drugs targeting these different aspects of RNA biology and introduce screen methods for discovering RNA-targeting small molecule drugs.

关 键 词：小分子药物 遗传疾病 RNA稳定性 RNA剪切 RNA翻译 药物筛选体系 

分 类 号：R914[医药卫生—药物化学]