Pharmacoproteomics: Mass spectrometry based method development for mechanism of action

药物效应的研究通常使用针对药物靶标的一系列特定的分析方法。例如，根据它们的靶标和一组其他的激酶来筛选激酶抑制剂。这种药物在细胞系统一级的全球效应往往没有得到研究，尤其是在药物开发的早期阶段。与进行这样的全球系统研究相关的成本和时间是限制因素。这是分析生物化学的一个有趣的方面，但还不发达。在这里，我们建议开发一种集成的分析系统，它将允许对药物治疗(药物蛋白质组学)做出反应的蛋白质组进行快速的全球研究。该系统将结合菲盖斯实验室开发的技术，允许每六小时对一种化合物进行药物蛋白质组筛选。质谱学将用于识别和量化数千种蛋白质，而生物信息学将用于根据预设标准对变化的蛋白质进行快速分类。如果成功，这个药物蛋白质组系统将加速药物的全球效应(S)的研究，并将有助于我们的工业合作伙伴快速筛选其化合物。

The study of drug effects is usually performed using a series of specific assays directed towards the drug target. For example, kinase inhibitors are screened against their targets and a panel of other kinases. The global effect of the drug at the cellular system level is often not studied and in particular not in the early stage of drug development. The cost and time associated with performing such global system studies are limiting factors. This is an interesting aspect of analytical biochemistry that is underdeveloped. Here we propose to develop an integrated analytical system that will allow rapid global study of the proteome in response to drug treatment (pharmacoproteomics). The system will combine technologies developed in the Figeys' laboratory that will allow pharmacoproteomic screening of one compound every six hours. Mass spectrometry will be used to identify and quantify 1000s of proteins while bioinformatics will be used to rapidly classify the proteins that change according to preset criteria. If successful, this pharmacoproteomic system would accelerate the study of the global effect(s) of drugs and be useful to our industrial partner for the rapid screening of their compounds.