DICP OpenIR
Subject Area物理化学
Glucuronidation of the broad-spectrum antiviral drug arbidol by UGT isoforms
Song, Jin-Hui1; Fang, Zhong-Ze2,5; Zhu, Liang-Liang4; Cao, Yun-Feng3; Hu, Cui-Min5; Ge, Guang-Bo4; Zhao, De-Wei1; De-Wei Zhao
KeywordArbidol Glucuronidation Udp-glucuronosyltransferases (Ugts)
Source PublicationJOURNAL OF PHARMACY AND PHARMACOLOGY
2013-04-01
DOI10.1111/jphp.12014
Volume65Issue:4Pages:521-527
Indexed BySCI
Cooperation Status
SubtypeArticle
Department18
Funding Project1806
Contribution Rank待补充
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Funding Organization4,3 ; 4,3 ; 4,3 ; 4,3
WOS SubjectPharmacology & Pharmacy
WOS Research AreaPharmacology & Pharmacy
WOS KeywordHUMAN UDP-GLUCURONOSYLTRANSFERASES ; MYCOPHENOLIC-ACID ; HUMAN LIVER ; IN-VITRO ; GENETIC POLYMORPHISMS ; VIRUS ; PHARMACOKINETICS ; IDENTIFICATION ; METABOLISM ; BIOACTIVATION
AbstractObjectives 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.
Language英语
Funding Organization4,3 ; 4,3 ; 4,3 ; 4,3
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WOS IDWOS:000316292000006
Citation statistics
Cited Times:21[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/119246
Collection中国科学院大连化学物理研究所
Corresponding AuthorDe-Wei Zhao
Affiliation1.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
Recommended Citation
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.,...&De-Wei Zhao.(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.
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