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药物研发中的蛋白质组学:新时代的曙光?

Proteomics in Drug Development: The Dawn of a New Era?

机构信息

Mosaiques Diagnostics GmbH, Rotenburger Straße 20, D-30659, Hannover, Germany.

BHF Glasgow Cardiovascular Research Centre, University of Glasgow, G12 8TA, Glasgow, UK.

出版信息

Proteomics Clin Appl. 2019 Mar;13(2):e1800087. doi: 10.1002/prca.201800087. Epub 2019 Feb 25.

Abstract

Mass spectrometry offers the potential of acquiring high resolution data depicting the functional status of a group of healthy or diseased individuals, according to different conditions. As most of the drugs are currently targeting proteins, proteomics has a dual value, both in the discovery of new molecules as therapeutic targets, but also as a methodology to perform high throughput drug profiling. As there is an evident need for drugs to be improved in terms of efficacy, a mechanistic insight for downstream effectors can be valuable in order to predict side effects and resistance mechanisms. Recently developed assays, like thermal proteome profiling enables comprehensive drug target profiling and is, therefore, of high value in drug discovery. In this review, a systematic literature search is conducted and the most prominent proteomics studies as implicated in assisting drug discovery and development is presented. Focus is placed on investigations that are closer to implementation, therefore particular emphasis is given in studies conducted in human diseased population and further verified in vitro or in vivo.

摘要

质谱分析具有获取描述不同条件下健康或患病个体群体功能状态的高分辨率数据的潜力。由于目前大多数药物都针对蛋白质,因此蛋白质组学具有双重价值,既是发现新分子作为治疗靶点的方法,也是进行高通量药物分析的方法。由于显然需要提高药物的疗效,因此对于下游效应器的机制见解可能具有价值,以便预测副作用和耐药机制。最近开发的测定法,如热蛋白质组学分析,可以进行全面的药物靶标分析,因此在药物发现中具有很高的价值。在本综述中,进行了系统的文献检索,并介绍了最突出的蛋白质组学研究,这些研究有助于药物发现和开发。重点放在更接近实施的研究上,因此特别强调在人类患病人群中进行的研究,并在体外或体内进一步验证。

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