诱导蛋白降解的小分子PROTACs的研究进展

Research progress in the study of small-molecule PROTACs induced protein degradation

利用小分子蛋白降解靶向嵌合体(PROTACs)诱导蛋白降解的新型肿瘤治疗策略能够通过细胞内泛素-蛋白酶体降解系统而调控靶蛋白水平,从而克服传统小分子抑制剂的缺陷。因此针对小分子PROTACs的设计、合成及表征成为当前药物化学研究的前沿之一。本文简介小分子PROTACs的功能及作用机制,着重综述小分子PROTACs的最新研究成果,展望其应用前景和亟需解决的问题。

The novel therapeutic strategy that can induce protein degradation by small molecular proteolytic targeting chimeras（PROTACs） offer a alternative approach with controling the target protein level through ubiquitinproteasome degradation system,which overcomes the defects of small molecular inhibitors. Therefore,the design,synthesis and characterization of PROTACs have become one of the most advanced projects in medicinal chemistry.In this paper,the function and mechanism of small molecule PROTACs are briefly introduced. The latest research progress of small molecular PROTACs are reviewed,and their applications and problems to be solved are prospected.