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基因组学、蛋白质组学和代谢组学在药物发现、开发及临床中的应用。

Application of genomics, proteomics and metabolomics in drug discovery, development and clinic.

作者信息

Russell Craig, Rahman Ayesha, Mohammed Afzal R

机构信息

Aston School of Pharmacy, Aston University, Birmingham, UK.

出版信息

Ther Deliv. 2013 Mar;4(3):395-413. doi: 10.4155/tde.13.4.

Abstract

Genomics, proteomics and metabolomics are three areas that are routinely applied throughout the drug-development process as well as after a product enters the market. This review discusses all three 'omics, reporting on the key applications, techniques, recent advances and expectations of each. Genomics, mainly through the use of novel and next-generation sequencing techniques, has advanced areas of drug discovery and development through the comparative assessment of normal and diseased-state tissues, transcription and/or expression profiling, side-effect profiling, pharmacogenomics and the identification of biomarkers. Proteomics, through techniques including isotope coded affinity tags, stable isotopic labeling by amino acids in cell culture, isobaric tags for relative and absolute quantification, multidirectional protein identification technology, activity-based probes, protein/peptide arrays, phage displays and two-hybrid systems is utilized in multiple areas through the drug development pipeline including target and lead identification, compound optimization, throughout the clinical trials process and after market analysis. Metabolomics, although the most recent and least developed of the three 'omics considered in this review, provides a significant contribution to drug development through systems biology approaches. Already implemented to some degree in the drug-discovery industry and used in applications spanning target identification through to toxicological analysis, metabolic network understanding is essential in generating future discoveries.

摘要

基因组学、蛋白质组学和代谢组学是在药物研发过程以及产品进入市场后经常应用的三个领域。本综述讨论了所有这三个“组学”,报告了每个领域的关键应用、技术、最新进展和期望。基因组学主要通过使用新型和下一代测序技术,通过对正常组织和患病组织的比较评估、转录和/或表达谱分析、副作用谱分析、药物基因组学以及生物标志物的识别,推动了药物发现和开发领域的发展。蛋白质组学通过包括同位素编码亲和标签、细胞培养中氨基酸的稳定同位素标记、相对和绝对定量的等压标签、多向蛋白质鉴定技术、基于活性的探针、蛋白质/肽阵列、噬菌体展示和双杂交系统等技术,在药物开发流程的多个领域得到应用,包括靶点和先导物识别、化合物优化、整个临床试验过程以及上市后分析。代谢组学虽然是本综述中考虑的三个“组学”中最新且发展最不完善的,但通过系统生物学方法为药物开发做出了重大贡献。代谢组学已经在一定程度上应用于药物发现行业,并用于从靶点识别到毒理学分析的各种应用中,理解代谢网络对于未来的发现至关重要。

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