Metabolic profiling of the anti-tumor drug regorafenib in mice
文献类型：期刊论文
| 作者 | Wang, Yi-Kun1,2; Xiao, Xue-Rong1; Xu, Kang-Ping3; Li, Fei1 |
| 刊名 | JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
 |
| 出版日期 | 2018-09-10 |
| 卷号 | 159页码:524-535 |
| 关键词 | Regorafenib Metabolomics Multiple mass defect filters Molecular docking |
| ISSN号 | 0731-7085 |
| DOI | 10.1016/j.jpba.2018.07.039 |
| 英文摘要 | Regorafenib is a novel tyrosine kinase inhibitor, which has been approved by the United States Food and DrugAdministration for the treatment of various tumors. The purpose of the present study was to describe the metabolic map of regorafenib, and investigate its effect on liver function. Mass spectrometry-based metabolomics approach integrated with multiple mass defect filter was used to determine the metabolites of regorafenib in vitro incubation mixtures (human liver microsomes and mouse liver microsomes), serum, urine and feces samples from mice treated with 80 mg/kg regorafenib. Eleven metabolites including four novel metabolites were identified in the present investigation. As halogen substituted drug, reductive defluorination and oxidative dechlorination metabolites of regorafenib were firstly report in present study. By screening using recombinant cytochrome P450 s (CYPs), CYP3A4 was found to be the principal isoforms involved in regorafenib metabolism. The predication with a molecular docking model confirmed that regorafenib had potential to interact with the active sites of CYP3A4, CYP3A5 and CYP2D6. Serum chemistry analysis revealed no evidence of hepatic damage from regorafenib exposure. This study provided a global view of regorafenib metabolism and its potential side-effects. (C) 2018 Elsevier B.V. All rights reserved. |
| 资助项目 | National Key Research and Development Program of China[2017YFC0906903] ; Kunming Institute of Botany[Y4662211K1] ; Thousand Young Talents Program of China |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000442699900058 |
| 出版者 | ELSEVIER SCIENCE BV |
| 资助机构 | National Key Research and Development Program of China ; Kunming Institute of Botany ; Thousand Young Talents Program of China |
| 源URL | [http://ir.kib.ac.cn/handle/151853/62223]  |
| 专题 | 中国科学院昆明植物研究所 |
| 通讯作者 | Li, Fei |
| 作者单位 | 1.Chinese Acad Sci, Kunming Inst Bot, States Key Lab Phytochem & Plant Resources West C, Kunming 650201, Yunnan, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Cent S Univ, Xiangya Sch Pharmaceut Sci, Changsha 410013, Hunan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Yi-Kun,Xiao, Xue-Rong,Xu, Kang-Ping,et al. Metabolic profiling of the anti-tumor drug regorafenib in mice[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2018,159:524-535. |
| APA | Wang, Yi-Kun,Xiao, Xue-Rong,Xu, Kang-Ping,&Li, Fei.(2018).Metabolic profiling of the anti-tumor drug regorafenib in mice.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,159,524-535. |
| MLA | Wang, Yi-Kun,et al."Metabolic profiling of the anti-tumor drug regorafenib in mice".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 159(2018):524-535. |
入库方式： OAI收割
来源：昆明植物研究所
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