Metabolic profiling of the anti-tumor drug regorafenib in mice

doi:10.1016/j.jpba.2018.07.039

KIB OpenIR

	Metabolic profiling of the anti-tumor drug regorafenib in mice
	Wang, Yi-Kun 1,2; Xiao, Xue-Rong 1; Xu, Kang-Ping 3; Li, Fei 1
	2018-09-10
发表期刊	JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
ISSN	0731-7085
卷号	159 页码:524-535
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.
关键词	Regorafenib Metabolomics Multiple mass defect filters Molecular docking
DOI	10.1016/j.jpba.2018.07.039
语种	英语
WOS记录号	WOS:000442699900058
引用统计	被引频次：19[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/62224
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.