药学学报, 2017, 52(9): 1379-1386
杨旭, 张翔. 分枝杆菌膜蛋白3抑制剂的研究进展[J]. 药学学报, 2017, 52(9): 1379-1386.
YANG Xu, ZHANG Xiang. Recent advances in study of mycobacterial membrane protein large 3 inhibitors[J]. Acta Pharmaceutica Sinica, 2017, 52(9): 1379-1386.

杨旭, 张翔
中国医学科学院、北京协和医学院药物研究所, 活性物质发现与适药化研究北京市重点实验室, 北京 100050
分枝杆菌膜蛋白3(mycobacterial membrane protein large 3,MmpL3)属于抗瘤细胞分裂(RND)蛋白超家族,它主要参与结核分枝杆菌中海藻糖单霉菌酸酯的转运过程,对MmpL3的抑制可以影响结核分枝杆菌细胞壁的合成。近年来,通过表型筛选已发现并确证了7类不同化学骨架的MmpL3抑制剂,拟用于耐药结核病的治疗。本文将简要论述这几类MmpL3抑制剂及其构效关系,介绍靶标确证的方法,并进一步探讨MmpL3抑制剂的作用机制。
关键词:    分枝杆菌膜蛋白3      结核分枝杆菌      构效关系      作用机制     
Recent advances in study of mycobacterial membrane protein large 3 inhibitors
Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China
Mycobacterial membrane protein large 3 (MmpL3) belongs to the resistance, nodulation and division (RND) superfamily whose role in mycobacteria is transporting trehalosemonomycolate (TMM). The inhibition of MmpL3 influences the formation of cell wall of mycobacteria. In the past few years, several whole cell-based screenings of compound libraries by different research groups has brought by a number of diverse chemical scaffolds active against Mycobacterium tuberculosis (Mtb). The aim of this review is to provide the recent advances in discovery of MmpL3 inhibitors with a special focus on the structure-activity relationship (SAR). Besides, this review will provide the information of target identification and the modes of action of the MmpL3 inhibitors.
Key words:    mycobacterial membrane protein large 3    Mycobacterium tuberculosis    structure-activity relationship    modes of action   
收稿日期: 2017-01-16
DOI: 10.16438/j.0513-4870.2017-0058
基金项目: 国家科技重大专项"重大新药创制"子课题2015ZX09102007"抗耐药结核新药TBI-001的临床前研究".
通讯作者: 张翔,Tel:86-10-63165248,E-mail:simon@imm.ac.cn
Email: simon@imm.ac.cn
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