The DOI matches its Crossref record; 61 of the 64 references it cites were found in a registry or an index.
Reactions and enzymes in the metabolism of drugs and other xenobiotics
Abstract
In this article, we offer an overview of the compared quantitative importance of biotransformation reactions in the metabolism of drugs and other xenobiotics, based on a meta-analysis of current research interests. Also, we assess the relative significance the enzyme (super)families or categories catalysing these reactions. We put the facts unveiled by the analysis into a drug discovery context and draw some implications. The results confirm the primary role of cytochrome P450-catalysed oxidations and UDP-glucuronosyl-catalysed glucuronidations, but they also document the marked significance of several other reactions. Thus, there is a need for several drug discovery scientists to better grasp the variety of drug metabolism reactions and enzymes and their consequences.
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“A recent meta-analysis (68) of the metabolic fate of .1000xenobiotics showed that cytochrome P450 catalyzed oxidations (40%) and UDP-glucuronosyltransferase glucuronidations (14%) were the most common followed by reactions involving dehydrogenases (8%), hydrolases (7%), glutathione-S-transferases (6%), and sulfatases (5%).”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [68]
In the citing paper
“The yield of phase I/II reactions are often very high (68,71), and host-transformed metabolites retain many of the features of their parent compounds.”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [68]
Citations
Cites
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Predicting in vivo drug interactions from in vitro drug discovery data
Wienkers, L. C., & Heath, T. G. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1851 · Cited by 910
Summary of information on human CYP enzymes: human P450 metabolism data
Rendić, S. (2002) · Drug Metabolism Reviews · doi:10.1081/dmr-120001392 · Cited by 819
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A Comprehensive Listing of Bioactivation Pathways of Organic Functional Groups
Kalgutkar, A. S. S., Gardner, I. B., Obach, R. S., Shaffer, C. L., Callegari, E., Henne, K. R., Mutlib, A. E., Dalvie, D., Lee, J. S., Nakai, Y., et al. (2005) · Current Drug Metabolism · doi:10.2174/1389200054021799 · Cited by 623
Evolution of the P450 gene superfamily:
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MetaSite: Understanding Metabolism in Human Cytochromes from the Perspective of the Chemist
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Cytochrome P450 Enzymes and Drug Metabolism in Humans
Zhao, M., Ma, J., Li, M., Zhang, Y., Jiang, B., Zhao, X., Huai, C., Shen, L., Zhang, N., He, L., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312808 · Cited by 1,070
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Bolton, J. L., & Dunlap, T. L. (2016) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.6b00256 · Cited by 538
The food metabolome: a window over dietary exposure
Scalbert, A., Brennan, L., Manach, C., Andres-Lacueva, C., Dragsted, L. O., Draper, J., Rappaport, S. M., van der Hooft, J. J., & Wishart, D. S. (2014) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.113.076133 · Cited by 519
Djoumbou-Feunang, Y., Fiamoncini, J., Gil-de-la-Fuente, A., Greiner, R., Manach, C., & Wishart, D. S. (2019) · Journal of Cheminformatics · doi:10.1186/s13321-018-0324-5 · Cited by 531
Metadata
- Authors
- Testa, B., Pedretti, A., & Vistoli, G.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- University of Milan (IT)
- Corresponding author
- Testa, Bernard
- Venue
- Drug Discovery Today
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 17
- Issue
- 11-12
- Pages
- 549-560
- ISSN
- 1359-6446 (ISSN-L)
- OpenAlex
- W2075550795
- Cited by
- 254
- References
- 64
- Citations by year
- 2026: 14 · 2025: 24 · 2024: 23 · 2023: 30 · 2022: 19 · 2021: 28 · 2020: 21 · 2019: 10 · 2018: 12 · 2017: 19 · 2016: 9 · 2015: 17 · 2014: 17 · 2013: 6 · 2012: 4
- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Discovery Today (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- drug metabolism, xenobiotic metabolism, cytochrome P450, UDP-glucuronosyltransferase, glucuronidation, drug-metabolizing enzymes, enzyme superfamilies, drug discovery
- MeSH terms
- Animals, Biochemical Phenomena, Pharmaceutical Preparations, Enzymes, Humans, Substrate Specificity, Xenobiotics, Molecular Structure, Metabolic Detoxication, Phase I, Metabolic Detoxication, Phase II, Drug Discovery, Drug-Related Side Effects and Adverse Reactions
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