Predominant contributions of carboxylesterase 1 and 2 in hydrolysis of anordrin in humans
文献类型：期刊论文
| 作者 | Jiang, Jinfang1,2; Chen, Xiaoyan1,2 ; Zhong, Dafang1,2
|
| 刊名 | XENOBIOTICA
 |
| 出版日期 | 2018 |
| 卷号 | 48期号:5页码:533-540 |
| 关键词 | Anordiol anordrin carboxylesterase drug-drug interaction hydrolysis in humans |
| ISSN号 | 0049-8254 |
| DOI | 10.1080/00498254.2017.1333658 |
| 文献子类 | Article |
| 英文摘要 | 1.Anordrin (2, 17-diethynyl-A-nor-5-androstane-2, 17-diol diproprionate) is post-coital contraceptive drug that is on the market in China for more than 30 years. This study aims to elucidate enzymes involved in anordrin hydrolysis, and to evaluate the significant role of carboxylesterases in anordrin hydrolysis in humans.2.Human liver and intestinal microsomes, recombinant human carboxylesterase were selected as enzyme sources. In human liver microsomes, intrinsic clearance was 68483L/min/mg protein, which was considerably higher than the value of intestine microsomes (94.613.3L/min/mg protein). Carboxylesterase (CES) 1 has more contribution than CES2 in human liver.3.Inhibition studies were performed using representative esterase inhibitors to confirm esterase isoforms involved in anordrin hydrolysis. Simvastatin strongly inhibited hydrolytic process of anordrin in liver and intestine microsomes, with IC50 values of 10.9 +/- 0.1 and 6.94 +/- 0.03M, respectively.4.The present study investigated for the first time hydrolytic enzyme phenotypes of anordrin. Anordrin is predominantly catalyzed by CES1 and CES2 to generate the main active metabolite, anordiol. Moreover, anordrin and its metabolite anordiol can be altered by esterase inhibitors, such as simvastatin, upon exposure in vivo. |
| WOS关键词 | HUMAN ARYLACETAMIDE DEACETYLASE ; HUMAN LIVER ; 17-ALPHA-DIETHYNYL-A-NOR-5-ALPHA-ANDROSTANE-2-BETA ; PHARMACOKINETICS ; 17-BETA-DIOL ; SIMVASTATIN ; 2-ALPHA ; ENZYME |
| 资助项目 | National Natural Science Foundation of China[81521005] |
| WOS研究方向 | Pharmacology & Pharmacy ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000426959200010 |
| 出版者 | TAYLOR & FRANCIS LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272329]  |
| 专题 | 上海药物代谢研究中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Zhong, Dafang |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Jiang, Jinfang,Chen, Xiaoyan,Zhong, Dafang. Predominant contributions of carboxylesterase 1 and 2 in hydrolysis of anordrin in humans[J]. XENOBIOTICA,2018,48(5):533-540. |
| APA | Jiang, Jinfang,Chen, Xiaoyan,&Zhong, Dafang.(2018).Predominant contributions of carboxylesterase 1 and 2 in hydrolysis of anordrin in humans.XENOBIOTICA,48(5),533-540. |
| MLA | Jiang, Jinfang,et al."Predominant contributions of carboxylesterase 1 and 2 in hydrolysis of anordrin in humans".XENOBIOTICA 48.5(2018):533-540. |
入库方式： OAI收割
来源：上海药物研究所
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