人细胞色素P450酶2J2的功能及其配体研究进展  

Research progress of human cytochrome P450 2J2 and its ligands

作　　者：马虹莹 宁静[2] 葛广波[2] 杨凌[2] 郝大程[1] 

机构地区：[1]大连交通大学环境化工学院/生物技术研究所,辽宁大连116028 [2]中国科学院大连化学物理研究所药用资源开发组,辽宁大连116023

出　　处：《药学学报》2017年第1期26-33,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81503152;81573501);辽宁省自然科学基金资助(2015020663);辽宁省研究生教育教学改革研究项目(2016)

摘　　要：细胞色素酶P450 2J2(cytochrome P450 2J2,CYP2J2)广泛分布于人体多个组织,参与众多内源性化合物和外源性药物的代谢。CYP2J2可催化花生四烯酸(arachidonic acid,AA)生成具有多种生理功能的环氧化二十碳三烯甘油酸(expoxyeicosatrienoic acids,EETs),进而在调节心血管功能和肿瘤发生发展中发挥重要作用。此外,CYP2J2在阿司咪唑、依巴斯汀和特非那定等临床药物的肠道代谢中也发挥关键作用,是多种药物肠道首过代谢环节的重要屏障。本综述结合国内外新近研究进展,系统介绍了CYP2J2的分布、功能及催化特征,CYP2J2功能的表征方法和探针底物研究现状、药物等外源物对CYP2J2的调节作用以及CYP2J2与人类疾病间的关系等,旨在使国内医药领域的研究者更加深入地了解CYP2J2的功能及其在疾病发生发展中的作用。本文通过对近年来CYP2J2配体(底物和抑制剂)研究进展的总结,以期为以CYP2J2为靶点的新药研发提供指导和参考。Cytochrome P4502J2 （CYP2J2） is widely distributed in various human tissues and takes a part in the metabolism of endogenous compounds and drugs. CYP2J2 can convert arachidonic acid （AA） to expoxyeicosatrienoie acids （EETs）, which have various biological effects, implying the important role of CYP2J2 in the regulation of cardiovascular system and promotion of tumor progression and metastasis. Additionally, CYP2J2 plays an indispensable role in the intestinal metabolism of various drugs, such as astemizole, terfenadine and ebastine. In this review, the metabolic function, characteristic of catalysis and tissue distribution of CYP2J2 are discussed with the latest literatures both in China and abroad. The state-of-the-art methods for characterization of CYP2J2 and current trend of substrate discovery as well as its relationship with disease are highlighted. This review gives in-depth understanding of the function of CYP2J2 and its role in disease advance. The information of ligand （substrate and inhibitor） will provide the theoretical guidance and reference to the development of novel drugs for CYP2J2.

关 键 词：CYP2J2 代谢 疾病 探针底物 CYP2J2抑制剂 

分 类 号：R963[医药卫生—微生物与生化药学]