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Interactions of Olomoucine II with Human Liver Microsomal Cytochromes P450
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SYSNO ASEP 0328733 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Interactions of Olomoucine II with Human Liver Microsomal Cytochromes P450 Title Interakce Olomoucinu II s lidským jaterním mikrozomálním cytochromem P450 Author(s) Siller, M. (CZ)
Anzenbacher, P. (CZ)
Anzenbacherová, E. (CZ)
Doležal, Karel (UEB-Q) RID, ORCID
Popa, Igor (UEB-Q)
Strnad, Miroslav (UEB-Q) RID, ORCIDSource Title Drug Metabolism and Disposition - ISSN 0090-9556
Roč. 37, č. 6 (2009), s. 1198-1202Number of pages 5 s. Language eng - English Country US - United States Keywords IN-VITRO ; BIOLOGICAL-ACTIVITY ; METABOLISM Subject RIV EB - Genetics ; Molecular Biology R&D Projects GA301/08/1649 GA ČR - Czech Science Foundation (CSF) GD303/09/H048 GA ČR - Czech Science Foundation (CSF) CEZ AV0Z50380511 - UEB-Q (2005-2011) UT WOS 000266147500008 DOI 10.1124/dmd.108.025502 Annotation Olomoucine II is a cyclin-dependent kinase inhibitor and a potential antineoplastic agent because it can arrest animal cell cycles. This study examines its interaction with human liver microsomal cytochrome P450 enzymes. Spectroscopic and HPLC methods were used to estimate the degree of olomoucine II-mediated inhibition of enzymatic activities of 8 drug-metabolizing P450s in vitro. In addition, HPLC-MS was used to identify an olomoucine II metabolite (2,5-dihydroxyroscovitine) formed in the reaction mixtures, and CYP3A4 was found to be responsible for the hydroxylation of the N6-benzyl ring at position 5, leading to this compound. Olomoucine II significantly inhibited the enzymatic activities of CYP1A2, CYP2A9 and (to a lesser degree) CYP3A4. Hence, the clinical relevance of these interactions should be carefully evaluated. Workplace Institute of Experimental Botany Contact David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Year of Publishing 2010
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