BioDetection Systems B.V., Science Park 406, 1098 XH Amsterdam, The Netherlands.
Division of Computational and Molecular Toxicology, Department of Chemistry and Pharmaceutical Sciences, Amsterdam Institute of Molecular and Life Sciences (AIMMs), Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.
Chem Res Toxicol. 2022 Jul 18;35(7):1184-1201. doi: 10.1021/acs.chemrestox.2c00067. Epub 2022 Jun 29.
The understanding of how exogenous chemicals (xenobiotics) are metabolized, distributed, and eliminated is critical to determine the impact of the chemical and its metabolites to the (human) organism. This is part of the research and educational discipline ADMET (absorption, distribution, metabolism, elimination, and toxicity). Here, we review the work of Jan Commandeur and colleagues who have not only made a significant impact in understanding of phase I and phase II metabolism of several important compounds but also contributed greatly to the development of experimental techniques for the study of xenobiotic metabolism. Jan Commandeur's work has covered a broad area of research, such as the development of online screening methodologies, the use of a combination of enzyme mutagenesis and molecular modeling for structure-activity relationship (SAR) studies, and the development of novel probe substrates. This work is the bedrock of current activities and brings the field closer to personalized (cohort-based) pharmacology, toxicology, and hazard/risk assessment.
了解外源性化学物质（xenobiotics）的代谢、分布和消除对于确定化学物质及其代谢物对（人类）机体的影响至关重要。这是 ADMET（吸收、分布、代谢、消除和毒性）研究和教育学科的一部分。在这里，我们回顾了扬·康芒德尔（Jan Commandeur）及其同事的工作，他们不仅对几种重要化合物的 I 相和 II 相代谢有了重要的认识，而且还为研究外源性化学物质代谢的实验技术的发展做出了巨大贡献。扬·康芒德尔的工作涵盖了广泛的研究领域，如在线筛选方法的开发、酶突变和分子建模组合用于构效关系（SAR）研究，以及新型探针底物的开发。这项工作是当前活动的基础，使该领域更接近个性化（基于队列）药理学、毒理学和危害/风险评估。
