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Tuberculosis Drug Discovery: Challenges and New Horizons
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2022-05-25 , DOI: 10.1021/acs.jmedchem.2c00227
Guilherme F S Fernandes 1 , Andrew M Thompson 2 , Daniele Castagnolo 1 , William A Denny 2 , Jean L Dos Santos 3
Affiliation  

Over the past 2000 years, tuberculosis (TB) has claimed more lives than any other infectious disease. In 2020 alone, TB was responsible for 1.5 million deaths worldwide, comparable to the 1.8 million deaths caused by COVID-19. The World Health Organization has stated that new TB drugs must be developed to end this pandemic. After decades of neglect in this field, a renaissance era of TB drug discovery has arrived, in which many novel candidates have entered clinical trials. However, while hundreds of molecules are reported annually as promising anti-TB agents, very few successfully progress to clinical development. In this Perspective, we critically review those anti-TB compounds published in the last 6 years that demonstrate good in vivo efficacy against Mycobacterium tuberculosis. Additionally, we highlight the main challenges and strategies for developing new TB drugs and the current global pipeline of drug candidates in clinical studies to foment fresh research perspectives.

中文翻译:

结核病药物发现:挑战和新视野

在过去的 2000 年中,结核病 (TB) 夺走的生命比任何其他传染病都多。仅在 2020 年,结核病就导致全球 150 万人死亡,与 COVID-19 造成的 180 万人死亡相当。世界卫生组织表示,必须开发新的结核病药物来结束这一流行病。在这一领域被忽视了几十年后,结核病药物发现的复兴时代已经到来,许多新的候选药物已进入临床试验。然而,虽然每年有数百种分子被报道为有前景的抗结核药物,但很少有人成功进入临床开发。在这篇文章中,我们批判性地回顾了过去 6 年发表的那些证明对结核分枝杆菌具有良好体内疗效的抗结核化合物. 此外,我们强调了开发新的结核病药物的主要挑战和战略,以及当前临床研究中候选药物的全球管道,以激发新的研究观点。
更新日期:2022-05-25
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