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	The molecular genetic analysis of fine needle aspiration biopsy samples of thyroid tumors Dvořáková, Klára ; Sýkorová, Vlasta (advisor) ; Grimmichová, Tereza (referee) Detailed record
	The molecular genetic analysis of fine needle aspiration biopsy samples of thyroid tumors Dvořáková, Klára ; Sýkorová, Vlasta (advisor) ; Grimmichová, Tereza (referee) Detailed record
	Metabolism of an inhibitor of tyrosine kinase lenvatinib as the anticancer drug with targeting effects Vavrová, Katarína ; Stiborová, Marie (advisor) ; Kubíčková, Božena (referee) Lenvatinib is an oral anticancer drug that belongs to a group of tyrosine kinases, which block signal pathway receptors for development and proliferation of various cancer diseases. Lenvatinib was approved in 2015 for a treatment of progressive, locally spread or metastatic, differentiated thyroid cancer refractory to radioiodine treatment. This thesis presents findings about the metabolism of lenvatinib and identification of enzymes responsible for biotransformation of this drug. Utilizing human and rat hepatic microsomes as well as recombinant cytochromes P450 (CYPs) expressed in SupersomesTM , the metabolism of lenvatinib was studied. Used rat microsomal systems were isolated from the liver of uninduced rats and from the liver of rats in which expression of individual CYPs was induced by CYP inducers. The lenvatinib metabolites were separated by HPLC and identified by mass spectroscopy. Using rat microsomal systems, O-desmethyllenvatinib and lenvatinib N-oxide were produced. The highest amount of these lenvatinib metabolites was produced by microsomes of rats pretreated with pregnenolone carbonitrile that is an inducer of CYP3A. Human hepatic microsomes oxidize lenvatinib to O-desmethyllenvatinib and N-descyklopropyllenvatinib. In the case of rat recombinant CYPs, O-desmethyllenvatinib was... Detailed record

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