Glucuronidation of the broad-spectrum antiviral drug arbidol by UGT isoforms

	Glucuronidation of the broad-spectrum antiviral drug arbidol by UGT isoforms
	Song, Jin-Hui 1; Fang, Zhong-Ze 2,5; Zhu, Liang-Liang 4; Cao, Yun-Feng 3; Hu, Cui-Min 5; Ge, Guang-Bo 4; Zhao, De-Wei 1
刊名	journal of pharmacy and pharmacology
	2013-04-01
卷号	65 期号:4 页码:521-527
关键词	arbidol glucuronidation UDP-glucuronosyltransferases (UGTs)
通讯作者	de-wei zhao
产权排序	待补充
合作状况	英
英文摘要	objectives the aim of this work was to identify the uridine glucuronosyltransferase (ugt) isoforms involved in the metabolism of the broad-spectrum antiviral drug arbidol. methods a human liver microsome (hlm) incubation system was employed to catalyse the formation of arbidol glucuronide. the glucuronidation activity of commercially recombinant ugt isoforms towards arbidol was screened. a combination of kinetic analysis and chemical inhibition study was used to determine the ugt isoforms involved in arbidol's glucuronidation. key findings the arbidol glucuronide was detected when arbidol was incubated with hlms in the presence of udp-glucuronic acid. the eadiehofstee plot showed that glucuronidation of arbidol was best fit to the michaelismenten kinetic model, and km and apparent vmax were calculated to be 8.0 +/- 0.7m and 2.03 +/- 0.05nmol/min/mg protein, respectively. assessment of a panel of recombinant ugt isoforms revealed that ugt1a1, ugt1a3 and ugt1a9 could catalyse the glucuronidation of arbidol. kinetic analysis and chemical inhibition study demonstrated that ugt1a9 was the predominant ugt isoform involved in arbidol glucuronidation in hlms. conclusions the major contribution of ugt1a9 towards arbidol glucuronidation was demonstrated in this study.
学科主题	物理化学
WOS标题词	science & technology ; life sciences & biomedicine
类目[WOS]	pharmacology & pharmacy
研究领域[WOS]	pharmacology & pharmacy
关键词[WOS]	human udp-glucuronosyltransferases ; mycophenolic-acid ; human liver ; in-vitro ; genetic polymorphisms ; virus ; pharmacokinetics ; identification ; metabolism ; bioactivation
收录类别	SCI
资助信息	4，3
原文出处	527
语种	英语
WOS记录号	WOS:000316292000006
公开日期	2014-09-11
内容类型	期刊论文
源URL	[http://159.226.238.44/handle/321008/119246]
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.Dalian Univ, Affiliated Zhongshan Hosp, Dept Orthoped, Dalian 116001, Peoples R China 2.Liaoning Med Univ, Jinzhou, Peoples R China 3.Shanghai Inst Planned Parenthood Res, Shanghai Engineer & Technol Res Ctr Reprod Hlth D, Key Lab Contracept & Devices Res NPFPC, Shanghai, Peoples R China 4.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China 5.NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA
推荐引用方式 GB/T 7714	Song, Jin-Hui,Fang, Zhong-Ze,Zhu, Liang-Liang,et al. Glucuronidation of the broad-spectrum antiviral drug arbidol by UGT isoforms[J]. journal of pharmacy and pharmacology,2013,65(4):521-527.
APA	Song, Jin-Hui.,Fang, Zhong-Ze.,Zhu, Liang-Liang.,Cao, Yun-Feng.,Hu, Cui-Min.,...&Zhao, De-Wei.(2013).Glucuronidation of the broad-spectrum antiviral drug arbidol by UGT isoforms.journal of pharmacy and pharmacology,65(4),521-527.
MLA	Song, Jin-Hui,et al."Glucuronidation of the broad-spectrum antiviral drug arbidol by UGT isoforms".journal of pharmacy and pharmacology 65.4(2013):521-527.