Activity of 2,6,9-trisubstituted purines as potent PDGFR alpha kinase inhibitors with antileukaemic activity

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F19%3A73598564" target="_blank" >RIV/61989592:15310/19:73598564 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0223523419308074" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0223523419308074</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejmech.2019.111663" target="_blank" >10.1016/j.ejmech.2019.111663</a>

Result language
angličtina
Original language name
Activity of 2,6,9-trisubstituted purines as potent PDGFR alpha kinase inhibitors with antileukaemic activity
Original language description
Receptor tyrosine kinase PDGFR alpha is often constitutively activated in various tumours and is regarded as a drug target. Here, we present a collection of 2,6,9-trisubstituted purines with nanomolar potency against PDGFR alpha and strong and selective cytotoxicity in the human eosinophilic leukaemia cell line EOL-1 that expresses the FIP1L1-PDGFRA oncogene. In treated EOL-1 cells, the example compound 14q inhibited the autophosphorylation of PDGFR alpha and the phosphorylation of STAT3 and ERK1/2. Interestingly, we observed pronounced and even increased effects of 14q on PDGFR alpha and some of its downstream signalling pathways after drug washout. In accordance with suppressed PDGFR alpha signalling, treated cells were arrested in the G1 phase of the cell cycle and eventually underwent apoptosis. Our results show that substituted purines can be used as specific modulators of eosinophilic leukaemia. (C) 2019 Elsevier Masson SAS. All rights reserved.
Czech name
—
Czech description
—

Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30107 - Medicinal chemistry

Project
<a href="/en/project/GA19-09086S" target="_blank" >GA19-09086S: Dual FLT3/CDK9 inhibition as a possible therapeutical approach for mixed lineage leukemia</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Similar results(10)