Activity of 2,6,9-trisubstituted purines as potent PDGFRα kinase inhibitors with antileukaemic activity
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00512138" target="_blank" >RIV/61388963:_____/19:00512138 - isvavai.cz</a>
Alternative codes found
RIV/61389030:_____/19:00512138
Result on the web
<a href="http://dx.doi.org/10.1016/j.ejmech.2019.111663" target="_blank" >http://dx.doi.org/10.1016/j.ejmech.2019.111663</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>
Alternative languages
Result language
angličtina
Original language name
Activity of 2,6,9-trisubstituted purines as potent PDGFRα kinase inhibitors with antileukaemic activity
Original language description
Receptor tyrosine kinase PDGFRα 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 PDGFRα 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 PDGFRα and the phosphorylation of STAT3 and ERK1/2. Interestingly, we observed pronounced and even increased effects of 14q on PDGFRα and some of its downstream signalling pathways after drug washout. In accordance with suppressed PDGFRα 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.
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
30205 - Hematology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
European Journal of Medicinal Chemistry
ISSN
0223-5234
e-ISSN
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Volume of the periodical
182
Issue of the periodical within the volume
Nov 15
Country of publishing house
FR - FRANCE
Number of pages
17
Pages from-to
111663
UT code for WoS article
000496896600073
EID of the result in the Scopus database
2-s2.0-85071911284