Bedaquiline in Drug-Resistant Tuberculosis: A Mini-Review.

IF 2.4 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current molecular pharmacology Pub Date : 2023-01-01 DOI:10.2174/1874467215666220421130707

Baljinder Singh, Charan Singh

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引用次数: 0

Abstract

Mycobacterium tuberculosis causes a contagious pulmonary disease with a high mortality rate in developing countries. However, the recommendation of DOTS (approved by WHO) was effective in treating tuberculosis, but nowadays, resistance from the first line (MDR-TB) and the second line (XDR-TB) drugs is highly common. Whereas, the resistance is a result of factors like poor patient constancy due to the long duration of therapy and co-infection with HIV. The approval of bedaquiline under an accelerated program for the treatment of MDR-TB has revealed its effectiveness in clinical trials as a therapeutic novel molecule. BDQ selectively inhibits the ATP synthase of bacterium and reduces ATP production. Additionally, the poor pharmacokinetic properties raised provocations in the MDR therapy, but the use of targeted drug delivery can solve the hurdles. While the preclinical and clinical studies included in this review are strongly suggesting the usefulness of BDQ in MDR-TB and XDR-TB, the repurposing of different drug classes in resistant TB is opening new opportunities to manage the disease conditions. In this review, we have summarized the examples of pipeline drugs and repurposed molecules with preclinical formulation developments.

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贝达喹啉治疗耐药结核病：微型综述。

结核分枝杆菌是一种传染性肺病，在发展中国家的死亡率很高。然而，世界卫生组织推荐的短期直接观察治疗（DOTS）对治疗结核病很有效，但如今，一线药物（MDR-TB）和二线药物（XDR-TB）的耐药性非常普遍。而耐药性的产生则是由于治疗时间过长导致患者耐受性差以及合并感染艾滋病毒等因素造成的。贝达喹啉（Bedaquiline）作为治疗 MDR-TB 的加速方案获得批准，显示了它作为一种新型治疗分子在临床试验中的有效性。BDQ 可选择性地抑制细菌的 ATP 合成酶，减少 ATP 的产生。此外，BDQ 药代动力学特性较差，给 MDR 治疗带来了挑战，但使用靶向给药可以解决这些障碍。本综述中的临床前和临床研究有力地证明了 BDQ 在 MDR-TB 和 XDR-TB 中的作用，而不同药物类别在耐药性结核病中的再利用也为控制病情带来了新的机遇。在本综述中，我们总结了临床前制剂开发的管线药物和再利用分子的实例。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current molecular pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery

CiteScore

4.90

自引率

3.70%

发文量

112

期刊介绍： Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology. Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.