New agents for the treatment of drug-resistant Mycobacterium tuberculosis.
New agents for the treatment of drug-resistant Mycobacterium tuberculosis.
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DOI：
10.1016/j.addr.2016.04.026
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发表时间：
2016-07-01
影响因子：
16.1
通讯作者：
Lee RE
中科院分区：
文献类型：
--
作者：
Hoagland DT;Liu J;Lee RB;Lee RE
剂量不足和不完整的治疗方案，加上结核杆菌能够引起对目前使用的药物耐受的潜伏感染，助长了耐多药结核病（MDR-TB）的兴起。耐多药结核感染的治疗是一个重大的临床挑战，几乎没有可行或有效的解决方案;因此，患者面临着预后不良和多年的治疗。本综述重点关注具有治疗耐多药结核病潜力的新兴药物类别，并强调其作为先导药物的特殊优势，包括其作用方式、体内疗效和关键药物化学性质。例子包括新批准的药物贝达喹啉和delaminid，以及临床和后期临床前开发管道中用于治疗耐多药结核病的其他药物。在此，我们讨论了开发治疗结核病的药物所面临的挑战，以及该领域如何适应这些困难，重点是可能产生更有效的药物和治疗方案的药物发现方法。
Inadequate dosing and incomplete treatment regimens, coupled with the ability of the tuberculosis bacilli to cause latent infections that are tolerant of currently used drugs, have fueled the rise of multidrug-resistant tuberculosis (MDR-TB). Treatment of MDR-TB infections is a major clinical challenge that has few viable or effective solutions; therefore patients face a poor prognosis and years of treatment. This review focuses on emerging drug classes that have the potential for treating MDR-TB and highlights their particular strengths as leads including their mode of action, in vivo efficacy, and key medicinal chemistry properties. Examples include the newly approved drugs bedaquiline and delaminid, and other agents in clinical and late preclinical development pipeline for the treatment of MDR-TB. Herein, we discuss the challenges to developing drugs to treat tuberculosis and how the field has adapted to these difficulties, with an emphasis on drug discovery approaches that might produce more effective agents and treatment regimens.