Mendel University in Brno - list of publications


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INDRA, R. -- POMPACH, P. -- VAVROVÁ, K. -- JÁKLOVÁ, K. -- HEGER, Z. -- ADAM, V. -- ECKSCHLAGER, T. -- ARLT, V M. -- STIBOROVÁ, M. Cytochrome P450 and flavin-containing monooxygenase enzymes are responsible for differential oxidation of the anti-thyroid-cancer drug vandetanib by human and rat hepatic microsomal systems. Environmental Toxicology and Pharmacology. 2020. v. 74, no. February, ISSN 1382-6689. URL: https://doi.org/10.1016/j.etap.2019.103310

Original name:
Cytochrome P450 and flavin-containing monooxygenase enzymes are responsible for differential oxidation of the anti-thyroid-cancer drug vandetanib by human and rat hepatic microsomal systems
Czech name:
Written by (author): Radek Indra
Mgr. Petr Pompach
Katarína Vavrová
Kateřina Jáklová
Mgr. Zbyněk Heger, Ph.D.
prof. RNDr. Vojtěch Adam, Ph.D.
Tomáš Eckschlager
Volker Manfred Arlt
Marie Stiborová
Department:
Department of Chemistry and Biochemistry
Kind of publication:
article in a professional periodical
Periodical:
Environmental Toxicology and Pharmacology
Nature of article:
paper
Volume no. (year):
74
Periodical number within the volume: February
Year of publication:
2020
Starting page:
Up to page:
Number of pages:
9
Sub-specification:
článek je obsažen v databázi Web of Science
UT code by Web of Science:
EID code by Scopus:
Form of publication:
printed version
Original language:
English
Description in original language:
We studied the in vitro metabolism of the anti-thyroid-cancer drug vandetanib in a rat animal model and demonstrated that N-desmethylvandetanib and vandetanib N-oxide are formed by NADPH- or NADH-mediated reactions catalyzed by rat hepatic microsomes and pure biotransformation enzymes. In addition to the structural characterization of vandetanib metabolites, individual rat enzymes [cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO)] capable of oxidizing vandetanib were identified. Generation of N-desmethylvandetanib, but not that of vandetanib N-oxide, was attenuated by CYP3A and 2C inhibitors while inhibition of FMO decreased formation of vandetanib N-oxide. These results indicate that liver microsomal CYP2C/3A and FMO1 are major enzymes participating in the formation of N-desmethylvandetanib and vandetanib N-oxide, respectively. Rat recombinant CYP2C11 > >3A1 > 3A2 > 1A1 > 1A2 > 2D1 > 2D2 were effective in catalyzing the formation of N-desmethylvandetanib. Results of the present study explain differences between the CYP- and FMO-catalyzed vandetanib oxidation in rat and human liver reported previously and the enzymatic mechanisms underlying this phenomenon.
Description in English:
Description in Czech:
Year of submission:
2020
Year of transmission:
RIV identification number:
URL:
https://doi.org/10.1016/j.etap.2019.103310
 
Entry made by:
Last change: 01/09/2020 14:24 (Markéta Hejčová, DiS.)

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Source specification:

Environmental Toxicology and Pharmacology. ISSN 1382-6689.

Original name:
Environmental Toxicology and Pharmacology
English name:
Czech name:
Written by (author):
Kind of publication:
magazine
ISSN:
1382-6689
Country of publisher:
Kingdom of the Netherlands
Place of publishing:
Publisher: Elsevier Science BV
URL:
Reviewed magazine:
no
Original language:
Description in original language:
Description in English:
Description in Czech:
 
Entry made by:
Last change: 03/14/2012 20:43 (Ing. Aleš Kutín)

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