Caldwell Gary W, Leo Gregory C
Janssen Research and Development, 1400 Welsh and McKean Roads, Spring House, PA 19477. United States.
Curr Top Med Chem. 2017;17(24):2716-2739. doi: 10.2174/1568026617666170707130032.
Untargeted metabolomics is a promising approach for reducing the significant attrition rate for discovering and developing drugs in the pharmaceutical industry. This review aims to highlight the practical decision-making value of untargeted metabolomics for the advancement of drug candidates in drug discovery/development including potentially identifying and validating novel therapeutic targets, creating alternative screening paradigms, facilitating the selection of specific and translational metabolite biomarkers, identifying metabolite signatures for the drug efficacy mechanism of action, and understanding potential drug-induced toxicity. The review provides an overview of the pharmaceutical process workflow to discover and develop new small molecule drugs followed by the metabolomics process workflow that is involved in conducting metabolomics studies. The pros and cons of the major components of the pharmaceutical and metabolomics workflows are reviewed and discussed. Finally, selected untargeted metabolomics literature examples, from primarily 2010 to 2016, are used to illustrate why, how, and where untargeted metabolomics can be integrated into the drug discovery/preclinical drug development process.
非靶向代谢组学是一种很有前景的方法，可降低制药行业在发现和开发药物过程中显著的淘汰率。本综述旨在强调非靶向代谢组学对于药物发现/开发中候选药物推进的实际决策价值，包括潜在地识别和验证新的治疗靶点、创建替代筛选模式、促进特异性和转化性代谢物生物标志物的选择、识别药物作用机制的代谢物特征以及了解潜在的药物诱导毒性。该综述首先概述了发现和开发新型小分子药物的制药流程工作流程，接着介绍了进行代谢组学研究涉及的代谢组学流程工作流程。对制药和代谢组学工作流程主要组成部分的优缺点进行了回顾和讨论。最后，选取了主要2010年至2016年的非靶向代谢组学文献实例，来说明非靶向代谢组学为何、如何以及在何处可整合到药物发现/临床前药物开发过程中。
