Pharmacoproteomics: Mass spectrometry based method development for mechanism of action

药物作用的研究通常使用一系列针对药物靶点的特异性测定来进行。例如，针对其靶标和一组其他激酶筛选激酶抑制剂。药物在细胞系统水平上的整体效应通常没有研究，特别是在药物开发的早期阶段。与进行这种全球系统研究有关的费用和时间是限制因素。这是分析生物化学的一个有趣的方面，但还没有得到充分的发展。在这里，我们建议开发一个集成的分析系统，将允许快速的全球性研究的蛋白质组药物治疗（药物蛋白质组学）。该系统将结合费格斯实验室开发的联合收割机技术，每六小时对一种化合物进行药物蛋白质组学筛选。质谱法将用于识别和定量1000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。如果成功的话，这种药物蛋白质组学系统将加速药物的全球效应的研究，并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.