{"title":"Non-P450 Drug-Metabolizing Enzymes: Contribution to Drug Disposition, Toxicity, and Development.","authors":"Tatsuki Fukami, Tsuyoshi Yokoi, Miki Nakajima","doi":"10.1146/annurev-pharmtox-052220-105907","DOIUrl":null,"url":null,"abstract":"<p><p>Most clinically used drugs are metabolized in the body via oxidation, reduction, or hydrolysis reactions, which are considered phase I reactions. Cytochrome P450 (P450) enzymes, which primarily catalyze oxidation reactions, contribute to the metabolism of over 50% of clinically used drugs. In the last few decades, the function and regulation of P450s have been extensively studied, whereas the characterization of non-P450 phase I enzymes is still incomplete. Recent studies suggest that approximately 30% of drug metabolism is carried out by non-P450 enzymes. This review summarizes current knowledge of non-P450 phase I enzymes, focusing on their roles in controlling drug efficacy and adverse reactions as an important aspect of drug development.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":11.2000,"publicationDate":"2022-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"16","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of pharmacology and toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-pharmtox-052220-105907","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/9/9 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 16
Abstract
Most clinically used drugs are metabolized in the body via oxidation, reduction, or hydrolysis reactions, which are considered phase I reactions. Cytochrome P450 (P450) enzymes, which primarily catalyze oxidation reactions, contribute to the metabolism of over 50% of clinically used drugs. In the last few decades, the function and regulation of P450s have been extensively studied, whereas the characterization of non-P450 phase I enzymes is still incomplete. Recent studies suggest that approximately 30% of drug metabolism is carried out by non-P450 enzymes. This review summarizes current knowledge of non-P450 phase I enzymes, focusing on their roles in controlling drug efficacy and adverse reactions as an important aspect of drug development.
期刊介绍：
Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.
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