Shanu-Wilson Julia, Evans Liam, Wrigley Stephen, Steele Jonathan, Atherton James, Boer Jason
Hypha Discovery Ltd., 154B Brook Drive, Milton Park, Abingdon, Oxfordshire OX14 4SD, U.K.
Incyte Corporation, 1801 Augustine Cut-off, Wilmington, Delaware 19803, United States.
ACS Med Chem Lett. 2020 Aug 28;11(11):2087-2107. doi: 10.1021/acsmedchemlett.0c00202. eCollection 2020 Nov 12.
Biotransformation has a huge impact on the efficacy and safety of drugs. Ultimately the effects of metabolism can be the lynchpin in the discovery and development cycle of a new drug. This article discusses the impact and application of biotransformation of drugs by mammalian systems, microorganisms, and recombinant enzymes, covering active and reactive metabolites, the impact of the gut microbiome on metabolism, and how insights gained from biotransformation studies can influence drug design from the combined perspectives of a CRO specializing in a range of biotransformation techniques and pharma biotransformation scientists. We include a commentary on how biology-driven approaches can complement medicinal chemistry strategies in drug optimization and the and surrogate systems available to explore and exploit biotransformation.
生物转化对药物的疗效和安全性有巨大影响。最终，代谢效应可能是新药发现和开发周期中的关键因素。本文讨论了哺乳动物系统、微生物和重组酶对药物进行生物转化的影响及应用，涵盖活性和反应性代谢物、肠道微生物群对代谢的影响，以及从生物转化研究中获得的见解如何从专注于一系列生物转化技术的合同研究组织（CRO）和制药生物转化科学家的综合角度影响药物设计。我们还对生物学驱动的方法如何在药物优化中补充药物化学策略，以及可用于探索和利用生物转化的替代系统进行了评论。
