N^(6)-甲基腺苷去甲基化酶小分子抑制剂的研究进展  

Progress of Small-Molecule Inhibitors of m^(6)A Demethylases

作　　者：汪香涵 徐俊 费文龙 尤启冬[1,2] 郭小可[1,2] WANG Xianghan;XU Jun;FEI Wenlong;YOU Qidong;GUO Xiaoke(Jiangsu Key Laboratory of Drug Design and Optimization,China Pharmaceutical University,Nanjing 211198,China;School of Pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学江苏省药物分子设计与成药性优化重点实验室,江苏南京211198 [2]中国药科大学药学院,江苏南京211198

出　　处：《药学进展》2023年第9期665-681,共17页Progress in Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(No.82173673)。

摘　　要：N^(6)-甲基腺苷(m^(6)A)是RNA中最常见、最保守的修饰之一,也是目前表观遗传学热门研究靶点之一。哺乳动物细胞中的m^(6)A修饰具有动态可逆性。m^(6)A的异常与多种疾病的形成、发展有关。m^(6)A去甲基化酶包括脂肪和肥胖相关蛋白(FTO)、Alkb家族同源蛋白5(ALKBH5)以及ALKBH3,负责催化RNA的m^(6)A去除甲基化。抑制m^(6)A去甲基化酶可调控m^(6)A的水平,并在相关癌症中降低细胞存活率从而抑制肿瘤生长。因此,针对m^(6)A去甲基化酶的小分子抑制剂研究成为抗肿瘤药物研究领域的热点。对m^(6)A去甲基化酶相关的癌症等疾病进行综述,着重关注其小分子抑制剂的研究进展,将有利于增进对该领域的全面认识并为相关药物的进一步研发提供参考。N^(6)-methyladenosine(m^(6)A)is one of the most common and conservative modifications in RNA,and is also a hot target in epigenetics research.The m^(6)A modification in mammalian is dynamic and reversible.The abnormality of m^(6)A is related to the formation and development of many diseases.The m^(6)A demethylation of RNA catalyzed by m^(6)A demethylases,including fat mass and obesity-associated proteins(FTO),Alkb Homologue 5(ALKBH5)and Alkb Homologue 3(ALKBH3).Inhibition of m6A demethylase can regulate the level of m^(6)A,reduce cell viability and inhibit tumor growth in associated cancers.The study of small molecule inhibitors targeting m^(6)A demethylase has become a hot topic in the field of anti-tumor drug research.This paper reviews the m^(6)A demethylase related diseases such as cancer and the research progress of various small molecule inhibitors of m^(6)A demethylases,which provides a basis for further research and development of related drugs.

关 键 词：表观遗传 N^(6)-甲基腺苷 RNA去甲基化酶 小分子抑制剂 

分 类 号：R914[医药卫生—药物化学] R979.1[医药卫生—药学]