Prospects for Antibacterial Discovery and Development.
Prospects for Antibacterial Discovery and Development.
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DOI：
10.1021/jacs.1c10200
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发表时间：
2021-12-22
影响因子：
15
通讯作者：
Khosla C
中科院分区：
文献类型：
--
作者：
Privalsky TM;Soohoo AM;Wang J;Walsh CT;Wright GD;Gordon EM;Gray NS;Khosla C
多重耐药细菌的日益流行是一场紧迫的健康危机，只能通过重新投资抗生素的发现和开发来应对。抗菌药物耐药性危机没有灵丹妙药；相反，需要采取多方面的方法。从这个角度来看，我们认为，面对不断变化的临床需求和支持技术，许多经过验证的抗菌靶点和相关的先导分子值得重新审视。与此同时，许多有价值的目标尽管含有可成药的活性位点，但缺乏良好的线索。创造性和启发性的技术支持发现工作；虽然土壤筛选工作经常导致抗生素的重新发现，但研究人员发现，通过研究未充分开发的生态位或利用基因组挖掘工作中的大量可用数据，可以成功地寻找新的抗生素先导物。明智地使用“多药理学”（即一种药物改变多个靶点活性的能力）也可以提供新的机会，继续寻找能够为旧抗生素注入新生命的耐药酶抑制剂也可以提供新的机会。最后，我们强调了用于抗菌药物发现和开发的可用药物经济学模型，同时为新模型提供了理由。
The rising prevalence of multi-drug resistant bacteria is an urgent health crisis that can only be countered through renewed investment in the discovery and development of antibiotics. There is no panacea for the antibacterial resistance crisis; instead, a multi-faceted approach is called for. In this perspective we make the case that, in the face of evolving clinical needs and enabling technologies, numerous validated antibacterial targets and associated lead molecules deserve a second look. At the same time, many worthy targets lack good leads despite harboring druggable active sites. Creative and inspired techniques buoy discovery efforts; while soil screening efforts frequently lead to antibiotic rediscovery, researchers have found success searching for new antibiotic leads by studying underexplored ecological niches or by leveraging the abundance of available data from genome mining efforts. The judicious use of “polypharmacology” (i.e., the ability of a drug to alter the activities of multiple targets) can also provide new opportunities, as can the continued search for inhibitors of resistance enzymes with the capacity to breathe new life into old antibiotics. We conclude by highlighting available pharmacoeconomic models for antibacterial discovery and development while making the case for new ones.
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影响因子：
3.7
作者：
Arvanitis M;Li G;Li DD;Cotnoir D;Ganley-Leal L;Carney DW;Sello JK;Mylonakis E
通讯作者：
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影响因子：
2.7
作者：
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DOI：
10.1007/s10295-005-0077-9
发表时间：
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影响因子：
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作者：
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通讯作者：
Baloch Z