In vitro and in silico studies of interaction of synthetic 2,6,9-trisubstituted purine kinase inhibitors BPA-302, BP-21 and BP-117 with liver drug-metabolizing cytochromes P450
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F20%3A73603436" target="_blank" >RIV/61989592:15110/20:73603436 - isvavai.cz</a>
Alternative codes found
RIV/61389030:_____/20:00541026
Result on the web
<a href="https://www.biomed.cas.cz/physiolres/pdf/2020/69_S627.pdf" target="_blank" >https://www.biomed.cas.cz/physiolres/pdf/2020/69_S627.pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.33549/physiolres.934611" target="_blank" >10.33549/physiolres.934611</a>
Alternative languages
Result language
angličtina
Original language name
In vitro and in silico studies of interaction of synthetic 2,6,9-trisubstituted purine kinase inhibitors BPA-302, BP-21 and BP-117 with liver drug-metabolizing cytochromes P450
Original language description
An evaluation of possible interactions with enzymes of drug metabolism (cytochromes P450, CYP) is an important part of studies on safety and, in general, on the properties of any drug or biologically active compound. The article is focused on the preliminary metabolic study of selected 2,6,9-trisubstituted purine kinase inhibitors with significant anticancer activities which we have developed. The compounds BP-21 and BP-117 represent strong CDK inhibitors and the compound BPA-302 was developed as selective FLT3-ITD kinase inhibitor. Here, emphasis is placed on interactions of these compounds with the nine most important forms of CYP to evaluate the possibility of inhibition of these enzymes. The possibility of their inhibitory effect was studied in vitro on selected human liver microsomal CYP enzymes. The most affected enzyme was CYP2C19. Its activity dropped to 22 % of its original value by BPA-302, to 13 % by BP-21 and to 6 % by BP-117 at the highest concentration tested (250 µmol·l-1). The results suggest that the metabolism of concomitantly administered drugs should not be significantly affected at lower doses. Molecular docking of BPA-302 indicated that it can bind to active site of both CYP2C19 and CYP2D6 enzymes above the heme cofactor corroborating the experimental data.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
PHYSIOLOGICAL RESEARCH
ISSN
0862-8408
e-ISSN
—
Volume of the periodical
69
Issue of the periodical within the volume
Suppl 4
Country of publishing house
CZ - CZECH REPUBLIC
Number of pages
10
Pages from-to
"'S626'"-"'S636'"
UT code for WoS article
000621838200009
EID of the result in the Scopus database
2-s2.0-85102232304