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Drug metabolism by flavin-containing monooxygenases of human and mouse

Phillips, IR; Shephard, EA; (2016) Drug metabolism by flavin-containing monooxygenases of human and mouse. Expert Opinion in Drug Metabolism and Toxicology , 13 (2) pp. 167-181. 10.1080/17425255.2017.1239718. Green open access

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Abstract

Introduction: Flavin-containing monooxygenases (FMOs) play an important role in drug metabolism. / Areas covered: We focus on the role of FMOs in the metabolism of drugs in human and mouse. We describe FMO genes and proteins of human and mouse; the catalytic mechanism of FMOs and their significance for drug metabolism; differences between FMOs and CYPs; factors contributing to potential underestimation of the contribution of FMOs to drug metabolism; the developmental and tissue-specific expression of FMO genes and differences between human and mouse; and factors that induce or inhibit FMOs. We discuss the contribution of FMOs of human and mouse to the metabolism of drugs and how genetic variation of FMOs affects drug metabolism. Finally, we discuss the utility of animal models for FMO-mediated drug metabolism in humans. / Expert opinion: The contribution of FMOs to drug metabolism may be underestimated. As FMOs are not readily induced or inhibited and their reactions are generally detoxifications, the design of drugs that are metabolized predominantly by FMOs offers clinical advantages. Fmo1(-/-),Fmo2(-/-),Fmo4(-/-) mice provide a good animal model for FMO-mediated drug metabolism in humans. Identification of roles for FMO1 and FMO5 in endogenous metabolism has implications for drug therapy and initiates an exciting area of research.

Type: Article
Title: Drug metabolism by flavin-containing monooxygenases of human and mouse
Open access status: An open access version is available from UCL Discovery
DOI: 10.1080/17425255.2017.1239718
Publisher version: http://dx.doi.org/10.1080/17425255.2017.1239718
Language: English
Additional information: This is an Accepted Manuscript of an article published by Taylor & Francis in Expert Opinion on Drug Metabolism & Toxicology on 29 September 2016, available online: http://www.tandfonline.com/10.1080/17425255.2017.1239718.
Keywords: Animal model, cytochrome P450, CYP, drug metabolism, flavin-containing monooxygenase, FMO, genetic variant, human, knockout mouse, mouse
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1517182
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