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Mycobacterial drug discovery
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2020-11-06 , DOI: 10.1039/d0md00261e
Katherine A. Abrahams 1, 2, 3, 4, 5 , Gurdyal S. Besra 1, 2, 3, 4, 5
Affiliation  

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.

中文翻译:

分枝杆菌药物的发现

结核分枝杆菌是肺结核的病原体。尽管有有效的治疗方案,但除了减少广泛的化疗时间和任何相关的毒性外,全球都在寻求新的抗结核药来应对不断发展的耐药性。分枝杆菌药物发现的途径可以从两个方向考虑:靶标到药物和药物到靶标。前一种方法使用常规方法,包括生化分析以及创新的计算屏幕,但由于缺乏全细胞活性,因此流失率很高,但尚未产生临床候选药物。在后一种方法中,针对化合物对细菌或模型生物的功效进行筛选,以确保整个细胞的活性,但是这里随后的目标识别是速率限制步骤。各种科学领域的进步已使两种方法在新型药物发现工具开发中的各个方面得以融合,现在它们已准备就绪,可加快发现具有已知靶点和全细胞活性的新型命中和潜在顾客的速度。这篇综述讨论了这些传统和创新技术,这些技术被广泛用于寻找新的抗结核化合物。
更新日期:2020-11-09
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