Trisubstituted Pyrazolopyrimidines as Novel Angiogenesis Inhibitors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F13%3A33148299" target="_blank" >RIV/61989592:15310/13:33148299 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61389030:_____/13:00395043

Výsledek na webu

<a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0054607" target="_blank" >http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0054607</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0054607" target="_blank" >10.1371/journal.pone.0054607</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Trisubstituted Pyrazolopyrimidines as Novel Angiogenesis Inhibitors

Popis výsledku v původním jazyce

Current inhibitors of angiogenesis comprise either therapeutic antibodies (e.g. bevacicumab binding to VEGF-A) or small molecular inhibitors of receptor tyrosin kinases like e.g. sunitinib, which inhibits PDGFR and VEGFR. We have recently identified cyclin-dependent kinase 5 (Cdk5) as novel alternative and pharmacologically accessible target in the context of angiogenesis. In the present work we demonstrate that trisubstituted pyrazolo[4,3-d]pyrimidines constitute a novel class of compounds which potently inhibit angiogenesis. All seven tested compounds inhibited endothelial cell proliferation with IC50 values between 1 and 18 mu M. Interestingly, this seems not to be due to cytotoxicity, since none of them showed acute cytotoxic effects on endothelialcells at a concentration of 10 mu M,. The three most potent compounds (LGR1404, LGR1406 and LGR1407) also inhibited cell migration (by 27, 51 and 31%, resp.), chemotaxis (by 50, 70 and 60% in accumulative distance, resp.), and tube forma

Název v anglickém jazyce

Trisubstituted Pyrazolopyrimidines as Novel Angiogenesis Inhibitors

Popis výsledku anglicky

Current inhibitors of angiogenesis comprise either therapeutic antibodies (e.g. bevacicumab binding to VEGF-A) or small molecular inhibitors of receptor tyrosin kinases like e.g. sunitinib, which inhibits PDGFR and VEGFR. We have recently identified cyclin-dependent kinase 5 (Cdk5) as novel alternative and pharmacologically accessible target in the context of angiogenesis. In the present work we demonstrate that trisubstituted pyrazolo[4,3-d]pyrimidines constitute a novel class of compounds which potently inhibit angiogenesis. All seven tested compounds inhibited endothelial cell proliferation with IC50 values between 1 and 18 mu M. Interestingly, this seems not to be due to cytotoxicity, since none of them showed acute cytotoxic effects on endothelialcells at a concentration of 10 mu M,. The three most potent compounds (LGR1404, LGR1406 and LGR1407) also inhibited cell migration (by 27, 51 and 31%, resp.), chemotaxis (by 50, 70 and 60% in accumulative distance, resp.), and tube forma

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

ED - Fyziologie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2013

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

PLoS One

ISSN

1932-6203

e-ISSN

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Svazek periodika

8

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

"e54607"

Kód UT WoS článku

000314707700068

EID výsledku v databázi Scopus

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