How Mycobacterium tuberculosis drug resistance has shaped anti-tubercular drug discovery.
How Mycobacterium tuberculosis drug resistance has shaped anti-tubercular drug discovery.
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DOI：
10.3389/fcimb.2022.974101
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发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
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作者：
耐药性是治疗结核病的一个日益严重的问题。在任何药物发现计划中，都需要考虑预先存在耐药性的临床分离株的流行情况。非特异性耐药机制，如增加外排或降低渗透性，需要考虑在开发个别候选药物和设计新的方案。我们回顾了许多不同的方法来开发新的类似物和药物组合或提高现有药物的疗效，这些药物可能会克服或延迟临床耐药性的出现。我们还讨论了需要充分表征现有药物的耐药和交叉耐药机制，以确保新药在临床上有效。
Drug resistance is an increasing problem for the treatment of tuberculosis. The prevalence of clinical isolates with pre-existing resistance needs to be considered in any drug discovery program. Non-specific mechanisms of resistance such as increased efflux or decreased permeability need to be considered both in developing individual drug candidates and when designing novel regimens. We review a number of different approaches to develop new analogs and drug combinations or improve efficacy of existing drugs that may overcome or delay the appearance of clinical resistance. We also discuss the need to fully characterize mechanisms of resistance and cross- resistance to existing drugs to ensure that novel drugs will be clinically effective.