Interactions of N-desmethyl imatinib, an active metabolite of imatinib, with P-glycoprotein in human leukemia cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F11%3A33118897" target="_blank" >RIV/61989592:15110/11:33118897 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s00277-010-1142-7" target="_blank" >http://dx.doi.org/10.1007/s00277-010-1142-7</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00277-010-1142-7" target="_blank" >10.1007/s00277-010-1142-7</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Interactions of N-desmethyl imatinib, an active metabolite of imatinib, with P-glycoprotein in human leukemia cells

Popis výsledku v původním jazyce

We measured intracellular accumulation of N-desmethyl imatinib (CGP 74588), the main pharmacologically active metabolite of imatinib (Gleevec or STI-571), in Bcr-Abl-positive cells. Using a sensitive and robust non-radioactive in vitro assay, we observedthat CGP74588 accumulates in significantly higher amount than imatinib in sensitive K562 cells. In contrast, the intracellular level of CGP74588 was significantly lower than that of imatinib in K562/Dox cells, which represent a multidrug-resistant variant of K562 cells due to the Pglycoprotein (P-gp, ABCB1, MDR1) overexpression. An in vitro enzyme-based assay provided evidence that CGP74588 might serve as an excellent substrate for Pgp. Accordingly, we found that CGP74588 up to 20 mýM concentration neither induced apoptosis nor inhibited substantially cell proliferation in resistant K562/Dox cells. In contrast, CGP74588 was capable to inhibit cell proliferation and induced apoptosis in sensitive K562 cells, although its effect was appr

Název v anglickém jazyce

Interactions of N-desmethyl imatinib, an active metabolite of imatinib, with P-glycoprotein in human leukemia cells

Popis výsledku anglicky

We measured intracellular accumulation of N-desmethyl imatinib (CGP 74588), the main pharmacologically active metabolite of imatinib (Gleevec or STI-571), in Bcr-Abl-positive cells. Using a sensitive and robust non-radioactive in vitro assay, we observedthat CGP74588 accumulates in significantly higher amount than imatinib in sensitive K562 cells. In contrast, the intracellular level of CGP74588 was significantly lower than that of imatinib in K562/Dox cells, which represent a multidrug-resistant variant of K562 cells due to the Pglycoprotein (P-gp, ABCB1, MDR1) overexpression. An in vitro enzyme-based assay provided evidence that CGP74588 might serve as an excellent substrate for Pgp. Accordingly, we found that CGP74588 up to 20 mýM concentration neither induced apoptosis nor inhibited substantially cell proliferation in resistant K562/Dox cells. In contrast, CGP74588 was capable to inhibit cell proliferation and induced apoptosis in sensitive K562 cells, although its effect was appr

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

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Projekt

<a href="/cs/project/NR9482" target="_blank" >NR9482: P-glykoprotein a jeho možný podíl na vzniku resistence vůči imatinibu u buněk exprimujících Bcr-Abl tyrosin kinázu</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2011

Kód důvěrnosti údajů

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

Název periodika

Annals of Hematology

ISSN

0939-5555

e-ISSN

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Svazek periodika

90

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

6

Strana od-do

837-842

Kód UT WoS článku

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EID výsledku v databázi Scopus

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