Metabolic effects of an aspartate aminotransferase-inhibitor on two T-cell lines
Metabolic effects of an aspartate aminotransferase-inhibitor on two T-cell lines
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DOI：
10.1371/journal.pone.0208025
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发表时间：
2018-12-07
期刊：
影响因子：
3.7
通讯作者：
Sellstedt, Magnus
中科院分区：
文献类型：
--
作者：
Antti, Henrik;Sellstedt, Magnus
一种新兴的方法来帮助阐明实验药物的作用模式是利用细胞系统的非靶向代谢组学。然而，这种筛选的解释是复杂的，需要更多的已知目标抑制剂的例子。本文用一种天冬氨酸转氨酶抑制剂处理了两株t细胞系，并用非靶向气相色谱-质谱法进行了分析。通过使用两种不同的细胞系增强了对数据的解释，并支持天冬氨酸转氨酶作为靶标。此外，这些数据表明对谷氨酸脱羧酶有意想不到的脱靶效应。这些结果证明了代谢组学的效力，为候选药物的作用模式和脱靶效应提供了见解。
An emerging method to help elucidate the mode of action of experimental drugs is to use untargeted metabolomics of cell-systems. The interpretations of such screens are however complex and more examples with inhibitors of known targets are needed. Here two T-cell lines were treated with an inhibitor of aspartate aminotransferase and analyzed with untargeted GC-MS. The interpretation of the data was enhanced by the use of two different cell-lines and supports aspartate aminotransferase as a target. In addition, the data suggest an unexpected off-target effect on glutamate decarboxylase. The results exemplify the potency of metabolomics to provide insight into both mode of action and off-target effects of drug candidates.