MmpL3 inhibitors as antituberculosis drugs
MmpL3 inhibitors as antituberculosis drugs
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DOI：
10.1016/j.ejmech.2020.112390
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发表时间：
2020-08-15
影响因子：
6.7
通讯作者：
Lu, Xiaoyun
中科院分区：
文献类型：
--
作者：
Shao, Min;McNeil, Matthew;Lu, Xiaoyun
分枝杆菌膜蛋白大3 （MmpL3）是一种内膜蛋白，可运输海藻糖-单菌酸，海藻糖-二菌酸和霉菌酸的前体，构成分枝杆菌外膜的基本成分。在体外和体内感染模型中，抑制MmpL3可削弱分枝杆菌细胞壁，最终导致细胞死亡。这突出了MmpL3作为药物靶点的治疗潜力。高通量全细胞筛选以及耐药突变体的全基因组测序已经确定了许多可归类为MmpL3抑制剂的化合物。在这篇综述中，我们提供了各种MmpL3抑制剂的当前发展情况，并讨论了该领域的潜在挑战。(C) 2020 Elsevier Masson SAS。版权所有。
The mycobacterial membrane protein Large 3 (MmpL3) is an inner membrane protein that transports trehalose-monomycolates, precursors for trehalose-dimycolates and mycolic acids that make up essential components of the mycobacterial outer membrane. Inhibition of MmpL3 weakens the mycobacterial cell wall and ultimately results in cell death in both in vitro and in vivo infection models. This highlights the therapeutic potential of MmpL3 as a drug target. High-throughput whole-cell screening along with whole genome sequencing of resistant mutants has identified numerous classes of compounds that can be classified as MmpL3 inhibitors. In this review, we provide insights into the current development of various MmpL3 inhibitors and discuss the potential challenges in this area. (C) 2020 Elsevier Masson SAS. All rights reserved.