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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FR - Pharmacology and apothecary chemistry

OECD FORD branch

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Project

<a href="/en/project/NR9482" target="_blank" >NR9482: P-glycoprotein and its possible contribution to development of resistance to Imatinib in Bcr-Abl expressing cells</a><br>

Continuities

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

Publication year

2011

Confidentiality

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

Name of the periodical

Annals of Hematology

ISSN

0939-5555

e-ISSN

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Volume of the periodical

90

Issue of the periodical within the volume

7

Country of publishing house

DE - GERMANY

Number of pages

6

Pages from-to

837-842

UT code for WoS article

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EID of the result in the Scopus database

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