Progress in the researches for antitumor NEDD8 activating enzyme inhibitors

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.