Show simple item record

dc.contributor.authorDehal, Shangara S.
dc.contributor.authorKupfer, David
dc.date2022-08-11T08:10:01.000
dc.date.accessioned2022-08-23T16:52:42Z
dc.date.available2022-08-23T16:52:42Z
dc.date.issued1999-06-01
dc.date.submitted2008-07-09
dc.identifier.citationDrug Metab Dispos. 1999 Jun;27(6):681-8.
dc.identifier.issn0090-9556 (Print)
dc.identifier.pmid10348797
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42107
dc.description.abstractEarlier study suggested that 3,4-dihydroxytamoxifen (tam catechol), a tamoxifen metabolite, is proximate to the reactive intermediate that binds covalently to proteins and possibly to DNA (). The current study demonstrates that rat and human hepatic cytochrome P-450s (CYPs) catalyze tam catechol formation from tamoxifen (tam), 3-hydroxy-tam (Droloxifene), and 4-hydroxy-tam (4-OH-tam). Higher levels of catechol were formed from 4-OH-tam and 3-hydroxy-tam than from tam. Evidence that human hepatic CYP3A4 and 2D6 catalyze the formation of tam catechol from 4-OH-tam and supportive data that the catechol is proximate to the reactive intermediate, was obtained: 1) There was a good correlation (r = 0.82; p
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=10348797&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dmd.aspetjournals.org/content/27/6/681.full.pdf+html
dc.subjectAnimals
dc.subjectBiotransformation
dc.subjectCatechols
dc.subjectCytochrome P-450 CYP2D6
dc.subjectCytochrome P-450 Enzyme System
dc.subjectEstrogen Antagonists
dc.subjectHumans
dc.subjectHydroxylation
dc.subjectLiver
dc.subjectMixed Function Oxygenases
dc.subjectPentobarbital
dc.subjectProtein Binding
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectTamoxifen
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.subjectPharmacology, Toxicology and Environmental Health
dc.titleCytochrome P-450 3A and 2D6 catalyze ortho hydroxylation of 4-hydroxytamoxifen and 3-hydroxytamoxifen (droloxifene) yielding tamoxifen catechol: involvement of catechols in covalent binding to hepatic proteins
dc.typeJournal Article
dc.source.journaltitleDrug metabolism and disposition: the biological fate of chemicals
dc.source.volume27
dc.source.issue6
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/491
dc.identifier.contextkey544973
html.description.abstract<p>Earlier study suggested that 3,4-dihydroxytamoxifen (tam catechol), a tamoxifen metabolite, is proximate to the reactive intermediate that binds covalently to proteins and possibly to DNA (). The current study demonstrates that rat and human hepatic cytochrome P-450s (CYPs) catalyze tam catechol formation from tamoxifen (tam), 3-hydroxy-tam (Droloxifene), and 4-hydroxy-tam (4-OH-tam). Higher levels of catechol were formed from 4-OH-tam and 3-hydroxy-tam than from tam. Evidence that human hepatic CYP3A4 and 2D6 catalyze the formation of tam catechol from 4-OH-tam and supportive data that the catechol is proximate to the reactive intermediate, was obtained: 1) There was a good correlation (r = 0.82; p</p>
dc.identifier.submissionpathoapubs/491
dc.contributor.departmentDepartment of Pharmacology and Molecular Toxicology
dc.contributor.departmentWorcester Foundation for Biomedical Research
dc.source.pages681-8


This item appears in the following Collection(s)

Show simple item record