非P450酶介导的药物氧化代谢研究进展

发布时间：2018-03-22 12:24

本文选题：黄素单氧化酶　切入点：单胺氧化酶　出处：《药学学报》2017年01期 　论文类型：期刊论文

【摘要】：常见的催化药物氧化代谢的非P450酶包括黄素单氧化酶(FMO)、单胺氧化酶(MAO)、醛氧化酶(AO)、黄嘌呤氧化酶(XO)、乙醇脱氢酶(ADH)和乙醛脱氢酶(ALDH)。近年来,它们在药物氧化代谢中的作用越来越受到重视。但是,由于在药物发现和先导化合物优化过程中通常使用P450酶相关的体外模型进行代谢研究,非P450酶在药物氧化代谢中的贡献往往被低估。本文综述了以上非P450酶的催化反应类型、常见底物、基因多态性以及药物相互作用,并总结了非P450酶介导药物氧化代谢的体外研究模型及影响因素。与P450酶类似,非P450酶可以直接催化药物发生氧化代谢,产生具有治疗活性的代谢物或者毒性代谢物。这类酶也可以进一步氧化经P450酶催化产生的毒性代谢物,发挥解毒作用。与P450酶相比,大部分非P450酶(如FMO和MAO)不容易被诱导。
[Abstract]:Common non-P450 enzymes that catalyze the oxidative metabolism of drugs include FMOO, MAOG, AOO, XOO, ADH) and ALDH. Their role in drug oxidation metabolism has been paid more and more attention. However, due to the use of P450 enzyme related in vitro models for metabolic studies in drug discovery and lead compound optimization, The contribution of non-P450 enzymes to drug oxidative metabolism is often underestimated. The types of catalytic reactions, common substrates, gene polymorphisms and drug interactions of these non-P450 enzymes are reviewed. The research model of non-P450 enzyme mediated drug oxidation metabolism in vitro and its influencing factors were summarized. Similar to P450 enzyme, non-P450 enzyme can directly catalyze the oxidative metabolism of drugs. These enzymes can further oxidize the toxic metabolites catalyzed by P450 enzymes and play a detoxification effect. Compared with P450 enzymes, most non-P450 enzymes (such as FMO and Mao) are not easily induced.
【作者单位】：中国科学院上海药物研究所;
【基金】：国家自然科学基金资助项目(81573500)
【分类号】：R96

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