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Stereoselective interactions of warfarin enantiomers with the pregnane X nuclear receptor in gene regulation of major drug-metabolizing cytochrome P450 enzymes
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SYSNO ASEP 0355208 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Stereoselective interactions of warfarin enantiomers with the pregnane X nuclear receptor in gene regulation of major drug-metabolizing cytochrome P450 enzymes Author(s) Rulcová, A. (CZ)
Prokopová, I. (CZ)
Krausová, L. (CZ)
Bitman, M. (CZ)
Vrzal, R. (CZ)
Dvořák, Z. (CZ)
Blahoš, Jaroslav (UMG-J) RID
Pávek, P. (CZ)Source Title Journal of Thrombosis and Haemostasis - ISSN 1538-7933
Roč. 8, č. 12 (2010), s. 2708-2717Number of pages 10 s. Language eng - English Country GB - United Kingdom Keywords CYP3A4 ; gene regulation ; warfarin Subject RIV EB - Genetics ; Molecular Biology R&D Projects LC06063 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) CEZ AV0Z50520514 - UMG-J (2005-2011) UT WOS 000285110700016 DOI 10.1111/j.1538-7836.2010.04036.x Annotation Background: Warfarin, an antagonist of vitamin K, is an oral coumarin anticoagulant widely used to control and prevent thromboembolic disorders. Warfarin is clinically available as a racemic mixture of R- and S-warfarin. The S-enantiomer has three to five times greater anticoagulation potency than its optical congener. Recently, vitamin K-2 function has been proposed via the pregnane X receptor (PXR) in osteocytes. PXR acts as a xenobiotic sensor that controls expression of many genes involved in drug/xenobiotic metabolic clearance. Objective: The aim was to examine whether enantiomers of warfarin stereoselectively interact with PXR to up-regulate main drug/ xenobiotic-metabolizing enzymes of the cytochrome P450 superfamily. Methods: Interactions of warfarin enantiomers with PXR were tested by gene reporter assays and time-resolved fluorescence resonance energy transfer technology (TR-FRET) ligand binding assay. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2011
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