Cocktail探针药物法研究化合物PT-46的CYP酶系抑制作用  

CYP Enzymes Inhibitory Effects of PT-46 by Cocktail Probe Drug Method

作　　者：王丽丽 程飞 张娜娜 郑雪梅 张吉泉 陈瑞 WANG Li-li;CHENG Fei;ZHANG Na-na;ZHENG Xue-mei;ZHANG Ji-quan;CHEN Rui(Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D,Guizhou Medical University,Guizhou Guiyang 550025;College of Pharmacy,Guizhou Medical University,Guizhou Guiyang 550025,China)

机构地区：[1]贵州医科大学/贵州省化学合成药物研发利用工程技术研究中心,贵州贵阳550025 [2]贵州医科大学药学院,贵州贵阳550025

出　　处：《广州化工》2021年第21期38-42,共5页GuangZhou Chemical Industry

基　　金：国家自然科学基金(81703356);贵州省自然科学基金重点项目(黔科合基础[2020]1Z073);贵州省卫生计生委科学技术基金项目(gzwjkj2019-1-179);贵州省高等学校大学生创新训练计划项目(20195200128)。

摘　　要：考察抗肿瘤优选化合物PT-46对细胞色素P 450(CYP450)酶系的抑制作用,评价化合物潜在的药物相互作用。基于UPLC/MS分析方法,运用Cocktail探针底物法研究PT-46对体外人肝微粒体中5种常见CYP酶(CYP1A2、CYP2C9、CYP2C19、CYP2D6及CYP3A4)的抑制作用。结果表明,PT-46对人肝微粒体中CYP1A2、CYP2D6、CYP3A4等酶没有抑制作用,对CYP2C9及CYP2C19的抑制IC 50值分别为19.6μM及19.2μM,存在一定的抑制作用。本研究初步考察了PT-46潜在的药物相互作用,为该化合物的后期临床前研究提供参考。The inhibitory effect of PT-46,a preferred anti-tumor candidate,on the cytochrome P450(CYP)enzyme system was investigated,and its potential drug-drug interactions were evaluated.Based on UPLC/MS analysis,Cocktail probedrug method was used to study the inhibitory effect of PT-46 on five common CYP enzymes(CYP1A2,CYP2C9,CYP2C19,CYP2D6 and CYP3A4)in human liver microsomes in vitro.The results showed that PT-46 had no inhibitory effect on CYP1A2,CYP2D6 and CYP3A4 enzymes,while exhibited certain inhibitory effects on CYP2C9 and CYP2C19 enzymes with IC 50 values of 19.6 and 19.2μM,respectively.The potential drug-drug interactions of candidate PT-46 were investigated,which can provide a good reference for the further preclinical evaluation.

关 键 词：抗肿瘤药物 Cocktail探针底物法 肝微粒体 细胞色素P450酶系 代谢 

分 类 号：R979.1[医药卫生—药品]