Počet záznamů: 1
Trisubstituted purine inhibitors of PDGFR alpha and their antileukemic activity in the human eosinophilic cell line EOL-1
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SYSNO ASEP 0482957 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Trisubstituted purine inhibitors of PDGFR alpha and their antileukemic activity in the human eosinophilic cell line EOL-1 Tvůrce(i) Malínková, Veronika (UEB-Q) ORCID, RID
Řezníčková, Eva (UEB-Q) RID, ORCID
Jorda, Radek (UEB-Q) ORCID, RID
Gucký, T. (CZ)
Kryštof, Vladimír (UEB-Q) RID, ORCIDCelkový počet autorů 5 Zdroj.dok. Bioorganic & Medicinal Chemistry. - : Elsevier - ISSN 0968-0896
Roč. 25, č. 24 (2017), s. 6523-6535Poč.str. 13 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova dependent kinase inhibitors ; src tyrosine kinase ; 2,6,9-trisubstituted purines ; therapeutic target ; potent inhibitor ; imatinib ; leukemia ; mutations ; mutant ; domain Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Hematology CEP LO1204 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora UEB-Q - RVO:61389030 UT WOS 000415984900027 DOI 10.1016/j.bmc.2017.10.032 Anotace 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. Pracoviště Ústav experimentální botaniky Kontakt David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Rok sběru 2018
Počet záznamů: 1