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.
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)
出处
《广州化工》
CAS
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)。
