The tyrosine kinase inhibitor lenvatinib is oxidized by rat cytochromes P450 and affects their expression in rat liver

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F24%3A10494296" target="_blank" >RIV/00216208:11310/24:10494296 - isvavai.cz</a>
Alternative codes found
RIV/75010330:_____/24:00014706
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OTPFtFC3oU" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OTPFtFC3oU</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.2478/acph-2024-0027" target="_blank" >10.2478/acph-2024-0027</a>

Result language
angličtina
Original language name
The tyrosine kinase inhibitor lenvatinib is oxidized by rat cytochromes P450 and affects their expression in rat liver
Original language description
Lenvatinib is an orally effective tyrosine kinase inhibitor used to treat several types of tumors, including progressive, radioiodine-refractory differentiated thyroid cancer and advanced renal cell carcinoma. Although this drug is increasingly used in therapy, its metabolism and effects on the organism are still not described in detail. Using the rat as an experimental animal model, this study aimed to investigate the metabolism of lenvatinib by rat microsomal enzymes and cytochrome P450 (CYPs) enzymes recombinantly expressed in SupersomesTM in vitro and to assess the effect of lenvatinib on rat CYP expression in vivo. Two metabolites, O-desmethyl lenvatinib, and lenvatinib N-oxide, were produced by rat CYPs in vitro. CYP2A1 and 2C12 were found to be the most effective in forming O-desmethyl lenvatinib, while CYP3A2 was found to primarily form lenvatinib N-oxide. The administration of lenvatinib to rats caused changes in the expression of mRNA and protein, as well as the activity of various CYPs, particularly in an increase in CYP1A1. Thus, the administration of lenvatinib to rats has an impact on the level of CYPs.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology

Project
<a href="/en/project/GA18-10251S" target="_blank" >GA18-10251S: Comprehensive insight into mechanisms of action and metabolism of tyrosine kinase inhibitors and a study of ways increasing their antitumor efficiency</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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