Determination of antiprotozoal drug mechanisms by metabolomics approaches.
Determination of antiprotozoal drug mechanisms by metabolomics approaches.
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DOI：
10.1017/s0031182013000814
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发表时间：
2014-01
期刊：
影响因子：
2.4
通讯作者：
Barrett MP
中科院分区：
文献类型：
--
作者：
Creek DJ;Barrett MP
药物的发现、开发和最佳利用可以通过了解其作用方式而得到极大的加强。然而，目前市场上的许多药物通过未知的机制起作用。非靶向代谢组学提供了发现干扰细胞代谢的药物的作用模式的潜力。高分辨率LC-MS方法和改进的数据分析软件的开发现在允许以非靶向方式快速检测药物诱导的细胞代谢变化。一些研究已经证明了非靶向代谢组学为抗微生物药物，特别是抗原生动物药物提供无偏倚靶标发现的能力。此外，利用有针对性的代谢组学技术，使现有的假设，关于抗原虫药物机制的验证。代谢组学方法可能有助于通过确定药物靶点，并通过详细描述现有和新型抗原动物药物的作用模式和耐药性来优化新的候选药物。
The discovery, development and optimal utilization of pharmaceuticals can be greatly enhanced by knowledge of their modes of action. However, many drugs currently on the market act by unknown mechanisms. Untargeted metabolomics offers the potential to discover modes of action for drugs that perturb cellular metabolism. Development of high resolution LC-MS methods and improved data analysis software now allows rapid detection of drug-induced changes to cellular metabolism in an untargeted manner. Several studies have demonstrated the ability of untargeted metabolomics to provide unbiased target discovery for antimicrobial drugs, in particular for antiprotozoal agents. Furthermore, the utilization of targeted metabolomics techniques has enabled validation of existing hypotheses regarding antiprotozoal drug mechanisms. Metabolomics approaches are likely to assist with optimization of new drug candidates by identification of drug targets, and by allowing detailed characterization of modes of action and resistance of existing and novel antiprotozoal drugs.