基于Janus激酶和组蛋白去乙酰化酶的双靶点抑制剂研究进展  

Advances in research of dual inhibitors targeting Janus kinase and histone deacetylase

作　　者：沈婧 胡伟杰 董国强 盛春泉 黄亚辉 SHEN Jing;HU Wei-jie;DONG Guo-qiang;SHENG Chun-quan;HUANG Ya-hui(The Center for Basic Research and Innovation of Medicine and Pharmacy(MOE),School of Pharmacy,Second Military Medical University(Naval Medical University),Shanghai 200433,China;School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou 325035,China)

机构地区：[1]中国人民解放军海军军医大学药学院,教育部医药基础研究创新中心,上海200433 [2]温州医科大学药学院,浙江温州325035

出　　处：《药学学报》2024年第11期3057-3073,共17页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(82273779,82330109,22277138)。

摘　　要：Janus激酶(JAK)和组蛋白去乙酰化酶(histone deacetylase,HDAC)已被证实是自身免疫性疾病和肿瘤等多种疾病治疗中的重要靶标,至今已有多种JAK和HDAC抑制剂获批上市。近年来,基于网络药理学开发的单分子多靶点抑制(如JAK/HDAC双靶点抑制剂)在提高疗效、降低毒副作用和克服耐药性等方面取得重要进展。本文综述了新型JAK/HDAC双靶点抑制剂及基于JAK/HDAC的三靶点抑制剂,以期为开发新型JAK/HDAC多靶点抑制剂提供借鉴和参考。Janus kinase(JAK)and histone deacetylase(HDAC)referred to as crucial targets in autoimmune diseases and cancers have achieved quite success in the treatment of these diseases.Until now,several JAK and HDAC inhibitors have been approved.Recently,developing single multi-targeting inhibitors including JAK/HDAC dual inhibitors based on network pharmacology has made significant progress in improving therapeutic efficacy,reducing toxic and side effects,and overcoming drug resistance.In this review,we summarize novel JAK/HDAC dual inhibitors as well as JAK/HDAC-based triple-targeting inhibitors,in order to provide reference for the discovery of novel JAK/HDAC dual inhibitor.

关 键 词：JANUS激酶 组蛋白去乙酰化酶 双靶点抑制剂 构效关系 药效团 

分 类 号：R914[医药卫生—药物化学]