靶向SUMOylation通路的抗肿瘤小分子抑制剂研究进展

Research progress on targeted SUMOylation inhibitors and their antitumor activity

SUMOylation是一种重要的蛋白质翻译后修饰。与ubiquitylation类似,SUMOylation是指将小类泛素化修饰物(SUMO)蛋白特异性地共价连接到底物蛋白中的赖氨酸残基上的过程。SUMOylation通过调节底物蛋白的生物活性来调节细胞的生理功能及病理过程,在多种肿瘤的发生和发展中异常活化。因此,靶向SUMOylation已成为抗肿瘤药物研发的重要策略。本文总结了近年来靶向SUMOylation通路的小分子抑制剂研究的最新进展及其独特的抗肿瘤机制,其中包括SUMO活化酶E1(SAE)抑制剂、SUMO结合酶E2(UBC12)抑制剂及SUMO1降解剂。

SUMOylation is an important post-translational modification of proteins.Similar to ubiquitylation,SUMOylation is the process that the small ubiquitin-like modifier(SUMO)proteins are specifically and covalently binding to lysine residues of substrate proteins.Through SUMOylation,the physiological functions and pathological processes of cells are well controlled and balanced,and its abnormal activation has been reported in various tumors.Therefore,SUMOylation has been a potential target for anti-tumor drug development.In this review,we summarize recent advances on development of inhibitors targeting SUMOylation pathway and their antitumor properties.