Mycobacterial drug discovery.
Mycobacterial drug discovery.
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DOI：
10.1039/d0md00261e
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发表时间：
2020-11-06
影响因子：
4.1
通讯作者：
Besra GS
中科院分区：
文献类型：
--
作者：
Abrahams KA;Besra GS
结核分枝杆菌是肺结核病的病原体。尽管有有效的治疗方案，但全球都在寻求新的抗结核药物，以应对正在形成的耐药性威胁，同时减少化疗的持续时间和任何相关毒性。分枝杆菌药物发现的途径可以从两个方向考虑：靶向药物和药物靶向。前一种方法使用常规方法，包括生物化学测定沿着创新的计算筛选，但尚未产生任何药物候选人的临床，由于缺乏全细胞活性的高损耗率。在后一种方法中，筛选化合物文库对杆菌或模型生物体的功效，确保全细胞活性，但在此随后的靶标鉴定是限速步骤。在各种科学领域的进步已经使这两种方法在开发新药发现工具方面的融合成为可能，这些工具现在已经准备好加速发现具有已知靶点和全细胞活性的新型命中和先导物。本文综述了这些传统的和创新的技术，这些技术被广泛用于寻求新的抗结核化合物。创新的分枝杆菌药物发现，以加快确定新的候选药物与确认的目标和全细胞活性。
Mycobacterium tuberculosis is the causative pathogen of the pulmonary disease tuberculosis. Despite the availability of effective treatment programs, there is a global pursuit of new anti-tubercular agents to respond to the developing threat of drug resistance, in addition to reducing the extensive duration of chemotherapy and any associated toxicity. The route to mycobacterial drug discovery can be considered from two directions: target-to-drug and drug-to-target. The former approach uses conventional methods including biochemical assays along with innovative computational screens, but is yet to yield any drug candidates to the clinic, with a high attrition rate owing to lack of whole cell activity. In the latter approach, compound libraries are screened for efficacy against the bacilli or model organisms, ensuring whole cell activity, but here subsequent target identification is the rate-limiting step. Advances in a variety of scientific fields have enabled the amalgamation of aspects of both approaches in the development of novel drug discovery tools, which are now primed to accelerate the discovery of novel hits and leads with known targets and whole cell activity. This review discusses these traditional and innovative techniques, which are widely used in the quest for new anti-tubercular compounds. Innovations in mycobacterial drug discovery to accelerate the identification of new drug candidates with confirmed targets and whole cell activity.
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影响因子：
4.6
作者：
Cox JA;Mugumbate G;Del Peral LV;Jankute M;Abrahams KA;Jervis P;Jackenkroll S;Perez A;Alemparte C;Esquivias J;Lelièvre J;Ramon F;Barros D;Ballell L;Besra GS
通讯作者：
Besra GS
影响因子：
6.4
作者：
DeJesus MA;Gerrick ER;Xu W;Park SW;Long JE;Boutte CC;Rubin EJ;Schnappinger D;Ehrt S;Fortune SM;Sassetti CM;Ioerger TR
通讯作者：
Ioerger TR
影响因子：
82.9
作者：
Gandotra, Sheetal;Schnappinger, Dirk;Ehrt, Sabine
通讯作者：
Ehrt, Sabine
影响因子：
3.2
作者：
Gomez, JE;McKinney, JD
通讯作者：
McKinney, JD
影响因子：
5.3
作者：
Batt, Sarah M.;Cacho Izquierdo, Monica;Argyrou, Argyrides
通讯作者：
Argyrou, Argyrides