基于类泛素化信号通路NEDD8靶点的药物研究进展  

Research progress of NEDD8 inhibitors in neddylation signaling pathway

作　　者：郝蕊 杨心怡 钱峰[1] 叶德全[1] 孙磊[1] HAO Rui;YANG Xin-yi;QIAN Feng;YE De-quan;SUN Lei(Shanghai Jiaotong University,Shanghai 200240,China)

机构地区：[1]上海交通大学,上海200240

出　　处：《中国新药杂志》2018年第24期2888-2894,共7页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(31741038);国家自然科学基金资助项目(81770633)

摘　　要：类泛素化是与泛素类似的蛋白质修饰系统,可通过与底物蛋白结合改变其生物化学性质。NEDD8是最重要的类泛素化蛋白之一,由于其与DNA破坏及细胞凋亡等密切相关,抑制类泛素化已被应用于多种疾病治疗中,尤其是抑制多种癌症细胞的增殖。随着对NEDD8研究的丰富,我们发现它在不同癌症中的底物蛋白及作用方式不同,同时,由于其还具有调控转录因子、调节树突状细胞反应等作用,类泛素化在多种炎症、细菌感染等疾病治疗中也可作为潜在靶点。本文对目前类泛素化信号通路NEDD8靶点的药物研究进展进行了详述。Neddylation is a protein modification system similar to ubiquitin that can change its biochemical properties through binding to substrate proteins.NEDD8 is one of the most important ubiquitin-like proteins. Because of its close relationship with DNA damage and apoptosis,inhibition of neddylation has been applied in the treatment of many diseases,especially the proliferation of various cancer cells.With more and more research of NEDD8,we found that its substrate proteins and modes of action are different in different cancers.At the same time,due to its role in regulating dendritic cells and transcription factors,neddylation can also be used as potential targets of a variety of inflammation,bacterial infections and other diseasess.This article illustrated the current research progress of the inhibitors of NEDD8.

关 键 词：类泛素化 抑制剂 MLN4924 

分 类 号：R967[医药卫生—药理学]