A tyrosine kinase inhibitor lenvatinib is oxidized by human cytochromes P450 and aldehyde oxidase in vitro

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216305%3A26620%2F18%3APU136064" target="_blank" >RIV/00216305:26620/18:PU136064 - isvavai.cz</a>

Výsledek na webu

<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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Jazyk výsledku

angličtina

Název v původním jazyce

A tyrosine kinase inhibitor lenvatinib is oxidized by human cytochromes P450 and aldehyde oxidase in vitro

Popis výsledku v původním jazyce

Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFR1-VEGFR3), fibroblast growth factor receptors (FGFR1-FGFR4), platelet-derived growth factor receptor (PDGFR) a, rearranged during transfection (RET), and v-kit (KIT) signalling networks implicated in tumor angiogenesis. It is used for treatment of certain tumors of the thyroid gland and metastatic renal cell carcinoma. Based on preliminary studies using human hepatic microsomes, lenvatinib was suggested to be oxidized by cytochromes P450 (CYPs), mainly by CYP3A4, to its O-demethylated metabolite, a desmethylated form of lenvatinib. However, no direct prove of this suggestion was demonstrated. Therefore, the aim of this study was to investigate the metabolism of lenvatinib by human microsomal enzymes in vitro in detail. Utilizing human hepatic microsomes and recombinant CYPs expressed in Supersomes TM, the metabolism of lenvatinib was studied. The lenvatinib metabolites were separa

Název v anglickém jazyce

A tyrosine kinase inhibitor lenvatinib is oxidized by human cytochromes P450 and aldehyde oxidase in vitro

Popis výsledku anglicky

Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFR1-VEGFR3), fibroblast growth factor receptors (FGFR1-FGFR4), platelet-derived growth factor receptor (PDGFR) a, rearranged during transfection (RET), and v-kit (KIT) signalling networks implicated in tumor angiogenesis. It is used for treatment of certain tumors of the thyroid gland and metastatic renal cell carcinoma. Based on preliminary studies using human hepatic microsomes, lenvatinib was suggested to be oxidized by cytochromes P450 (CYPs), mainly by CYP3A4, to its O-demethylated metabolite, a desmethylated form of lenvatinib. However, no direct prove of this suggestion was demonstrated. Therefore, the aim of this study was to investigate the metabolism of lenvatinib by human microsomal enzymes in vitro in detail. Utilizing human hepatic microsomes and recombinant CYPs expressed in Supersomes TM, the metabolism of lenvatinib was studied. The lenvatinib metabolites were separa

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30204 - Oncology

Projekt

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Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů