Characterization of human cytochrome P450 isoforms involved in the metabolism of 7-epi-paclitaxel
文献类型：期刊论文
| 作者 | Zhang, Y. -Y.1,3; Liu, Y.1; Zhang, J. -W.1; Ge, G. -B.1; Wang, L. -M.2; Sun, J.2; Yang, L.1 |
| 刊名 | xenobiotica
 |
| 出版日期 | 2009 |
| 卷号 | 39期号:4页码:283-292 |
| 关键词 | 7-Epi-paclitaxel paclitaxel cytochrome P450 microsomes metabolism |
| 产权排序 | 1;1 |
| 通讯作者 | 杨凌 |
| 英文摘要 | the c-7 chiral centre in paclitaxel is subject to epimerization under physiological conditions, thus making 7-epi-paclitaxel as the principal degradant. this study was designed to characterize the cytochrome p450 (cyp) enzymes involved in 7-epi-paclitaxel metabolism, and to examine possible metabolic interactions that this c-7 epimer may have with paclitaxel. in human liver microsomes, 7-epi-paclitaxel was oxidized to two monohydroxylated metabolites while the metabolic sites occurred at the c-13 side-chain for m-1 and taxane core ring for m-2. a combination of correlation analysis, chemical inhibition studies, assays with recombinant cyps, and enzyme kinetics indicated that m-1 was generated predominantly by cyp3a4 and m-2 by cyp2c8. co-incubation of 7-epi-paclitaxel with paclitaxel in human liver microsomes resulted in potent inhibition of 6-hydroxypaclitaxel formation (ic50 = 2.1 0.2 m), thus decreasing the metabolic elimination of paclitaxel. in conclusion, both cyp3a4 and cyp2c8 play a major role in biotransformation of 7-epi-paclitaxel in human liver microsomes. the existence of epimeric interactions between paclitaxel and its degradant might be a noteworthy factor resulting in the complex pharmacokinetic profile of paclitaxel. |
| WOS标题词 | science & technology ; life sciences & biomedicine |
| 类目[WOS] | pharmacology & pharmacy ; toxicology |
| 研究领域[WOS] | pharmacology & pharmacy ; toxicology |
| 关键词[WOS] | ionization mass-spectrometry ; human liver-microsomes ; in-vitro metabolism ; liquid-chromatography ; regioselective metabolism ; taxol metabolism ; paclitaxel ; identification ; taxanes ; cancer |
| 收录类别 | SCI |
| 原文出处 | false |
| 语种 | 英语 |
| WOS记录号 | WOS:000265303000001 |
| 公开日期 | 2010-11-30 |
| 源URL | [http://159.226.238.44/handle/321008/101607]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 作者单位 | 1.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China 2.Dalian Med Univ, Affiliated Hosp 2, Dalian, Peoples R China 3.Chinese Acad Sci, Grad Sch, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Y. -Y.,Liu, Y.,Zhang, J. -W.,et al. Characterization of human cytochrome P450 isoforms involved in the metabolism of 7-epi-paclitaxel[J]. xenobiotica,2009,39(4):283-292. |
| APA | Zhang, Y. -Y..,Liu, Y..,Zhang, J. -W..,Ge, G. -B..,Wang, L. -M..,...&Yang, L..(2009).Characterization of human cytochrome P450 isoforms involved in the metabolism of 7-epi-paclitaxel.xenobiotica,39(4),283-292. |
| MLA | Zhang, Y. -Y.,et al."Characterization of human cytochrome P450 isoforms involved in the metabolism of 7-epi-paclitaxel".xenobiotica 39.4(2009):283-292. |
入库方式： OAI收割
来源：大连化学物理研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。