选择性免疫蛋白酶体抑制剂研究进展  

Research progress on selective immunoproteasome inhibitors

作　　者：孔丽敏[1] 陆婧怡 祝华建 张建康 KONG Limin;LU Jingyi;ZHU Huajian;ZHANG Jiankang(Department of Pharmacy,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China;School of Medicine,Zhejiang University City College,Hangzhou 310015,China)

机构地区：[1]浙江大学医学院附属第一医院药学部,浙江杭州310003 [2]浙江大学城市学院医学院,浙江杭州310015

出　　处：《浙江大学学报（医学版）》2019年第6期688-694,共7页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金(81803432);浙江省基础公益研究计划(LGF18H300001)

摘　　要：免疫蛋白酶体与血液肿瘤、感染性疾病、自身免疫性疾病、中枢神经系统疾病等密切相关,这些疾病均呈现免疫蛋白酶体高表达。免疫蛋白酶体抑制剂可通过抑制相关细胞诱导因子的生成和自身反应性T细胞的活性来阻断免疫蛋白酶体的表达,从而治疗相关疾病。选择性免疫蛋白酶体抑制剂研发的关键是针对免疫型蛋白酶体的高度选择性,兼顾蛋白酶体上三个活性亚基的活性水平,才能在达到良好疗效的同时减少不良反应。本文介绍了免疫蛋白酶体的结构、功能,以及与多种疾病之间的关系,针对目前已报道的环氧酮肽类共价结合、其他短肽类共价结合、短肽类非共价结合选择性免疫蛋白酶体抑制剂的结构、活性及发展现状作一综述。Immunoproteasome is associated with various diseases such as hematologic malignancies,inflammatory,autoimmune and central nervous system diseases,and over expression of immunoproteasome is observed in all of these diseases.Immunoproteasome inhibitors can reduce the expression of immunoproteasome by inhibiting the production of related cell-inducing factors and the activity of T lymphocyte for treating related diseases.In order to achieve good efficacy and reduce the toxic effects,key for development of selective immunoproteasome inhibitors is the high selectivity and potent activity of the three active subunits of the proteasome.This review summarizes the structure and functions of immunoproteasome and the associated diseases.Besides,structure,activity and status of selective immunoproteasome inhibitors are also been highlighted.

关 键 词：半胱氨酸内肽酶类/分析 多酶复合物 构效关系 自身免疫疾病 蛋白酶体抑制剂/治疗 硼替佐米 综述 

分 类 号：R94[医药卫生—药剂学] R967[医药卫生—药学]