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Research advances in non-P450-mediated drug oxidative metabolism
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Lei ZHOU, Da-fang ZHONG*, Xiao-yan CHEN
Acta Pharmaceutica Sinica | 2017, 52(1) : 8 - 18
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Acta Pharmaceutica Sinica | 2017, 52(1): 8-18
• SPECIAL REPORTS •
Research advances in non-P450-mediated drug oxidative metabolism
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Lei ZHOU, Da-fang ZHONG*, Xiao-yan CHEN
Affiliations
  • Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Published: 2017-01-12 doi: 10.16438/j.0513-4870.2016-1005
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The major non-P450 enzymes involved in the oxidative metabolism of drugs are:the flavincontaining monooxygenase (FMO), the monoamine oxidase (MAO), the aldehyde oxidase (AO), the xanthine oxidase (XO), the alcohol dehydrogenase (ADH) and the aldehyde dehydrogenase (ALDH). In recent years, the role of non-P450 enzymes in drug oxidative metabolism has garnered increasing attention. However, the contribution of non-P450 enzymes to the drug oxidative metabolism is possibly underestimated in many cases, as most metabolism studies in drug discovery and lead optimization are conducted using in vitro test systems related to P450 enzymes. In this article, these non-P450 enzymes in terms of catalyzed reaction types, common substrates, gene polymorphism and drug interaction are reviewed, and the in vitro models and factors for non-P450-mediated oxidative metabolism are summarized. Similar to P450 enzymes, non-P450 enzymes can directly catalyze the oxidation of drugs, yielding therapeutically active metabolites or toxic metabolites. These enzymes can also oxidize the toxic metabolites, generated from P450-catalyzed reaction, to nontoxic metabolites. In general, most non-P450 enzymes (such as FMO and MAO) appear to be much less inducible than P450 enzymes.

flavin-containing monooxygenase  /  monoamine oxidase  /  aldehyde oxidase  /  xanthine oxidase  /  alcohol dehydrogenase  /  aldehyde dehydrogenase  /  oxidative metabolism
Lei ZHOU, Da-fang ZHONG, Xiao-yan CHEN. Research advances in non-P450-mediated drug oxidative metabolism[J]. Acta Pharmaceutica Sinica, 2017 , 52 (1) : 8 -18 . DOI: 10.16438/j.0513-4870.2016-1005
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doi: 10.16438/j.0513-4870.2016-1005
  • Receive Date：2016-10-17
  • Online Date：2026-01-14
  • Published：2017-01-12
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  • Received：2016-10-17
  • Revised：2016-12-09
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    Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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