Oxidation of a tyrosine kinase inhibitor vandetanib by human cytochromes P450 and flavin monooxygenases in vitro and its effect of DNA adduct formation mediated by an anticancer drug ellipticine
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216305%3A26620%2F18%3APU136048" target="_blank" >RIV/00216305:26620/18:PU136048 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1002/2211-5463.12453" target="_blank" >https://doi.org/10.1002/2211-5463.12453</a>
DOI - Digital Object Identifier
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Alternative languages
Result language
angličtina
Original language name
Oxidation of a tyrosine kinase inhibitor vandetanib by human cytochromes P450 and flavin monooxygenases in vitro and its effect of DNA adduct formation mediated by an anticancer drug ellipticine
Original language description
Vandetanib is a tyrosine kinase inhibitor (TKI) used for treatment of certain tumors of the thyroid gland. It inhibits signalling of epidermal growth, vascular endothelial growth factor or rearranged during transfection. Here, using human hepatic microsomes and recombinant cytochromes P450 (CYPs) and flavincontaining monooxygenases (FMOs) expressed in Supersomes TM, oxidation of vandetanib was studied. The vandetanib metabolites were separated by HPLC and identified by mass spectroscopy. Human hepatic microsomes oxidize vandetanib to N-desmethyl-vandetanib, but not to vandetanib-N-oxide. Of all tested human CYP enzymes, the CYP1A1, 2C8, 2D6, 3A4 and 3A5 enzymes, mainly in the presence of cytochrome b5, oxidize vandetanib to N-desmethylvandetanib. No vandetanib-N-oxide was generated by tested human CYPs. However, FMO enzymes were able to generate this metabolite. Of three human FMOs tested (FMO1, FMO3 and FMO5), FMO1 and FMO3 oxidize vandetanib to vandetanib-N-oxide. FMO1 was more effective than FMO3
Czech name
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Czech description
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Classification
Type
O - Miscellaneous
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů