抗肿瘤NEDD8活化酶抑制剂的研究进展

Progress in the researches for antitumor NEDD8 activating enzyme inhibitors

NEDD8活化酶(NAE)是Neddylation过程中的限速酶,抑制NAE的活性,能够降低泛素-蛋白酶体系统(UPS)通路的活性和相关蛋白的降解,诱导肿瘤细胞凋亡。与蛋白酶体抑制剂相比,NAE抑制剂对干扰细胞内环境稳态更有特异性。随着对NAE研究的不断深入,多种NAE抑制剂已被报道。根据这些NAE抑制剂的结构特点,可分为AMP类似物、双黄酮类脱氧鸭嘴花碱酮衍生物和金属铑络合物类等。本文介绍了类泛素化修饰Neddylation过程,其限速酶NAE与肿瘤的生理作用,并综述了NAE抑制剂的最新研究进展。

Inhibition of NEDD8 activating enzyme（NAE）,the rate limiting enzyme in Neddylation,can suppress the activity of ubiquitin-proteasome system（UPS） pathway and decrease degradations of related proteins,resulting in cell apoptosis.Compared with the proteasome inhibitors,NAE inhibitors can interfere with cellular homeostasis with more specificity.With the rapid development of the research on NAE,a variety of NAE inhibitors have been reported.According to the structure characteristics,NAE inhibitors can be divided into the AMP analogues,double flavonoids deoxidization duckbill alkali ketone derivatives and metal rhodium complex classes,etc.The process of ubiquitinated modified Neddylation,NAE and physiological role of tumor has been introduced in this paper,and the latest progress of NAE inhibitors also has been summarized.