Trisubstituted purine inhibitors of PDGFR alpha and their antileukemic activity in the human eosinophilic cell line EOL-1

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F17%3A00482957" target="_blank" >RIV/61389030:_____/17:00482957 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15310/17:73584379
Result on the web
<a href="http://dx.doi.org/10.1016/j.bmc.2017.10.032" target="_blank" >http://dx.doi.org/10.1016/j.bmc.2017.10.032</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bmc.2017.10.032" target="_blank" >10.1016/j.bmc.2017.10.032</a>

Result language
angličtina
Original language name
Trisubstituted purine inhibitors of PDGFR alpha and their antileukemic activity in the human eosinophilic cell line EOL-1
Original language description
Inhibition of protein kinases is a validated concept for pharmacological intervention in cancers. Many kinase inhibitors have been approved for clinical use, but their practical application is often limited. Here, we describe a collection of 23 novel 2,6,9-trisubstituted purine derivatives with nanomolar inhibitory activities against PDGFR alpha, a receptor tyrosine kinase often found constitutively activated in various tumours. The compounds demonstrated strong and selective cytotoxicity in the human eosinophilic leukemia cell line EOL-1, whereas several other cell lines were substantially less sensitive. The cytotoxicity in EOL-1, which is known to express the FIP1L1-PDGFR alpha fusion gene encoding an oncogenic kinase, correlated significantly with PDGFR alpha inhibition. EOL-1 cells treated with the compounds also exhibited dose-dependent inhibition of PDGFR alpha autophosphorylation and suppression of its downstream signaling pathways with concomitant G1 phase arrest, confirming the proposed mechanism of action. Our results show that substituted purines can be used as platforms for preparing tyrosine kinase inhibitors with specific activity towards eosinophilic leukemia.
Czech name
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Czech description
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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

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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