靶向核酸的小分子药物研究进展

Research Progress of Small Molecular Drugs Targeting Nucleic Acids

核酸是细胞内最重要的生物大分子之一,负责遗传信息的携带与传递并参与细胞命运调控。氮芥是美国食品药品监督管理局批准的首个抗肿瘤药物。这类核酸烷化剂以及随后出现的多类直接作用于核酸的分子是早年药物研发的热点方向。但是,因其选择性以及毒性等问题,在近代很长一段时间内,靶向核酸的小分子药物发展相当缓慢。随着现代对核酸结构、功能及其作用机制的进一步揭示,基于新型核酸靶标以及药物设计技术开展创新药物研究重新受到重点关注。综述对这一领域近年来上市或已进入临床试验的代表性分子进行了总结,以期为靶向核酸的小分子药物研发提供参考。

Nucleic acid,one of the most important biological macromolecules in cells,plays a crucial role in the carrying and transmission of genetic information and participates in the regulation of cell fate.Nitrogen mustard was the first anti-tumor drug approved by the U.S.Food and Drug Administration.This type of nucleic acid alkylating agent and the subsequent development of many types of molecules acting directly on nucleic acids became hot topics in drug research and development in the early years.However,due to problems such as selectivity and toxicity,the development of nucleic acid-targeting drug molecules has been quite slow over a long period of time.With the further revelation of the structures,functions and mechanisms of action of nucleic acids in recent years,innovative drug research based on new nucleic acid targets and drug design strategies has regained our attention.This review summarizes recent advancements in this field,encompassing approved molecules and those under clinical trials,so as to provide insights for the development of small molecule drugs targeting nucleic acids.