吡咯里嗪类非甾体抗炎药ML-3000衍生物对人P450同工酶的体外抑制作用  

In vitro inhibition of ML-3000 derivatives in non-steroidal anti-inflammatory drugs of pyrrolizine on human cytochrome P450 isozymes

作　　者：崔涛[1,2] 曾勇[2] 梅林雨[2] 高晶[2] 伊秀林[2] 司端运[2] 

机构地区：[1]天津中医药大学,天津300193 [2]天津药物研究院天津市新药安全评价研究中心,天津300193

出　　处：《药物评价研究》2013年第4期249-252,共4页Drug Evaluation Research

摘　　要：目的研究吡咯里嗪类ML-3000及其两种NO供体衍生物ML-4000和ML-5000对人P450同工酶CYP2D6、CYP1A2、CYP2C9、CYP2C19和CYP3A4的体外抑制作用。方法采用Gentest公司的高通量P450酶抑制剂筛选试剂盒(High throughput Inhibitor Screening Kit),测定ML-3000、ML-4000和ML-5000对五种P450同工酶CYP2D6、CYP1A2、CYP2C9、CYP2C19和CYP3A4的体外抑制作用。结果 ML-3000、ML-4000和ML-5000抑制CYP3A4的IC50分别为7.07、0.40、2.82μmol/L,对其他4个酶(CYP1A2、CYP2D6、CYP2C9和CYP2C19)的IC50均大于10μmol/L。结论 3种化合物对CYP3A4活力均有抑制作用,其中ML-4000的抑制能力最强。3种化合物对其他4个酶基本没有抑制作用。Objective To investigate the inhibition of ML-3000 and two NO donor derivatives in pyrrolizine on five human cytochrome P450 isozymes CYP2D6, CYP1A2, CYP2C9, CYP2C19, and CYP3A4. Methods Inhibition ofML-3000, ML-4000, and ML-5000 on five human cytochrome P450 isozymes CYP2D6, CYP1A2, CYP2C9, CYP2C19, and CYP3A4 was determined with High Throughput Inhibitor Sceening Kit. Results IC50 values ofML-3000, ML-4000, and ML-5000 to CYP3A4 were 7.07, 0.40, and 2.82 μmol/L, respectively. IC50 values ofML-3000, ML-4000, and ML-5000 to others were more than 10μmol/L. Conclusion Three compounds have the inhibitory effects on CYP3A4. Among them, ML-4000 has the strongest inhibition. The three compounds show no inhibition on the other four enzymes.

关 键 词：肝细胞色素P450 NO供体化合物 IC50 

分 类 号：R969.2[医药卫生—药理学]