代谢组学在药物研发中的应用进展

Progress in the application of metabonomics in drug development

代谢组学是对生物体内代谢通路上下游小分子代谢物进行定性定量研究,寻找代谢网络与生理病理变化的对应关系。这些小分子参与机体活动,在产生生理病理效应或者信号传导等过程中具有重要作用。代谢组的变化展示了生物体目前正在发生的改变,反映基因变化和环境影响后的综合结果。研究代谢物模式的显著变化已被公认为可以了解药物开发的关键方面,如药物疗效和毒性,将代谢组学纳入组学研究平台使我们更接近于定义表型,并能够寻找改善疾病诊断的替代方法。研究代谢组学的分析策略和统计工具的进步,在药物开发的早期阶段能防止药物失败,并减少Ⅱ期和Ⅲ期临床试验的财务损失。本文介绍代谢组学以及代谢组学在药物开发过程中的应用进展,并讨论其未来发展方向和面临的挑战。

Metabolomics is a qualitative and quantitative study of small molecule metabolites in the upstream and downstream of metabolic pathways in organisms to find the corresponding relationship between metabolic network and physiological and pathological changes.These small molecules participate in body activities and play an important role in the process of producing physiological and pathological effects or signal transduction.Changes in the metabolome show changes that are currently occurring,reflecting a combination of genetic changes and environmental influences.Studying significant changes in metabolite patterns has been recognized as a tool for understanding key aspects in drug development,such as drug efficacy and toxicity.The inclusion of metabolomics in the omics research platform brings us closer to defining phenotypes and allows us to look for alternative ways to improve the disease diagnosis.Advances in analytical strategies and statistical tools for studying metabolomics allow us to prevent drug failures at the early stages of drug development and reduce the financial losses of expensive phaseⅡandⅢclinical trials.This article introduces metabonomics and some examples of its application in drug development,and discusses its future directions and challenges.