Changing the Rules of TB-Drug Discovery
Changing the Rules of TB-Drug Discovery
复制标题
DOI：
10.1021/acs.jmedchem.9b01716
复制
发表时间：
2019-12-12
影响因子：
7.3
通讯作者：
Cox, Jonathan A. G.
中科院分区：
文献类型：
--
作者：
Harrison, James;Cox, Jonathan A. G.
新靶点新药的发现对于结核病(TB)治疗的持续成功至关重要，因为结核病人群中耐药感染的流行率越来越高。结核分枝杆菌富马酸水合酶(Mtb)富马酸水合酶(富马酸酶)是一种高度保守的必需蛋白质，与人类富马酸酶具有相同的活性部位，因此活性部位抑制对细菌和人类都具有同等的细胞毒性。最近发现了一系列新的Mtb抑制化合物，通过与非保守的变构位点结合来靶向Mtb-富马酸酶，这是一个重大进展，为消除抗生素发现教条提供了进一步的证据，即保守的蛋白质不是良好的抗生素靶点。
The discovery of new drugs with novel targets is paramount to the continued success of tuberculosis (TB) treatment due to the increasing prevalence of antibiotic resistant infections in the TB population. Mycobacterium tuberculosis (Mtb) fumarate hydratase (fumarase) is a highly conserved essential protein that shares an active site with human fumarase, making active site inhibition equally cytotoxic for both bacteria and humans. The recent discovery of a set of new Mtb inhibitory compounds that target Mtb-fumarase by binding to a nonconserved allosteric site is a major advancement, providing further evidence to dispel the antibiotic discovery dogma that conserved proteins do not make good antibiotic targets.