摘要
磺酸化代谢(又称硫酸化代谢)在药物的体内处置中发挥重要作用,是新药研发以及临床合理用药的重要基础。人磺基转移酶(又称硫酸转移酶)包含4个家族13个亚型,在体内具有广泛的底物,主要分布于肝、小肠、肾和肺等器官。对大多数底物而言,磺基转移酶介导的代谢常呈现典型的底物抑制特征;而低底物浓度水平通常会诱导酶的表达。体内磺酸化代谢由磺基转移酶催化小分子化合物结合3′-磷酸腺苷-5′-磷酸硫酸酯提供的磺酸基完成。一般情况下,磺酸化代谢介导药物或外源性异物的解毒过程,但在特殊药物代谢中产生毒性或不良反应。笔者综述了近年来磺基转移酶及磺酸化代谢在药物研究中的进展,以期为药物代谢的研究、新药研发与临床用药提供参考。
Sulfonation metabolism plays an important role in the disposition of drugs in vivo,which are significantly influencing the development of new drugs and the rational application of drugs in the clinic practice.Human sulfotransferases(SULTs)are currently divided into 13 subtypes from 4 families,with a wide range of substrates in the body.They are mainly distributed in the liver,small intestine,kidney and lung.In addition,SULTs expression can be induced by various substrates,and most substrates can inhibit sulfotransferase to a certain extent at high concentrations.In vivo,sulfonation metabolism is catalyzed by the binding of sulfuryl group,which is provided by 3′-adenosine-5′-phosphoryl sulfate,to the xenobiotic or endobiotic substrates.In most cases,sulfonation leads to the detoxification and facilitate the excretion of substrates,whereas toxicity or adverse reactions in the metabolism of specific drugs.The later cases normally involve formation of chemically reactive metabolites.This article reviews the recent progress of SULTs and sulfonation in drug research and development,which may gain insights into the understanding of roles of SULTs and sulfonation in drug metabolism and safety assessment,thus facilitate development of new drugs and clinical drug usage.
作者
黄昊妍
任光辉
傅可嘉
赵娣
陈西敬
张永杰
HUANG Hao-yan;REN Guang-hui;FU Ke-jia;ZHAO Di;CHEN Xi-jing;ZHANG Yong-jie(Clinical Pharmacokinetics Laboratory,School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Nanjing 211198,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2021年第3期169-174,共6页
Chinese Pharmaceutical Journal
基金
国家自然科学基金项目资助(81473272,81503148,82003877)
中央高校基本科研业务费专项资金项目资助(2632018PT02,2632020ZD01)
中国药科大学“双一流”创新团队项目资助(CPU2018GY29,CPU2018GF11)
江苏省自然科学基金项目资助(BK20190557)。
关键词
磺基转移酶
磺酸化代谢
药物代谢
诱导与抑制
解毒与致毒
sulfotransferase
sulfonation
drug metabolism
induction and inhibition
detoxification and toxicity
