Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois.
Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois.
Transl Res. 2020 Jun;220:68-97. doi: 10.1016/j.trsl.2020.03.007. Epub 2020 Mar 16.
The current tuberculosis (TB) predicament poses numerous challenges and therefore every incremental scientific work and all positive socio-political engagements, are steps taken in the right direction to eradicate TB. Progression of the late stage TB-drug pipeline into the clinics is an immediate deliverable of this global effort. At the same time, fueling basic research and pursuing early discovery work must be sustained to maintain a healthy TB-drug pipeline. This review encompasses a broad analysis of chemotherapeutic strategies that target the DNA replication, protein synthesis, cell wall biosynthesis, energy metabolism and proteolysis of Mycobacterium tuberculosis (Mtb). It includes a status check of the current TB-drug pipeline with a focus on the associated biology, emerging targets, and their promising chemical inhibitors. Potential synergies and/or gaps within or across different chemotherapeutic strategies are systematically reviewed as well.
当前的结核病（TB）困境带来了诸多挑战，因此每一项科学工作的进展和所有积极的社会政治参与，都是朝着消除结核病方向迈出的正确步骤。将晚期结核病药物研发管道推进到临床应用是这一全球努力的直接成果。与此同时，必须持续推动基础研究和早期发现工作，以保持健康的结核病药物研发管道。这篇综述广泛分析了针对结核分枝杆菌（Mtb）DNA 复制、蛋白质合成、细胞壁生物合成、能量代谢和蛋白水解的化学治疗策略。它还检查了当前的结核病药物研发管道的现状，重点关注相关生物学、新出现的靶点及其有前途的化学抑制剂。还系统地审查了不同化学治疗策略内部或之间的潜在协同作用和/或差距。
