Characterization of a Pyrazolo[4,3-d]pyrimidine Inhibitor of Cyclin-dependent Kinases 2 and 5 and Aurora A With Pro-Apoptotic and Anti-Angiogenic Activity In Vitro
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F15%3A33157571" target="_blank" >RIV/61989592:15310/15:33157571 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/61389030:_____/15:00454968
Výsledek na webu
<a href="http://onlinelibrary.wiley.com/doi/10.1111/cbdd.12618/epdf" target="_blank" >http://onlinelibrary.wiley.com/doi/10.1111/cbdd.12618/epdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1111/cbdd.12618" target="_blank" >10.1111/cbdd.12618</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Characterization of a Pyrazolo[4,3-d]pyrimidine Inhibitor of Cyclin-dependent Kinases 2 and 5 and Aurora A With Pro-Apoptotic and Anti-Angiogenic Activity In Vitro
Popis výsledku v původním jazyce
Selective inhibitors of kinases that regulate the cell cycle, such as cyclin-dependent kinases (CDKs) and aurora kinases, could potentially become powerful tools for the treatment of cancer. We prepared and studied a series of 3,5,7-trisubstituted pyrazolo[4,3-d]pyrimidines, a new CDK inhibitor scaffold, to assess their CDK2 inhibitory and antiproliferative activities. A new compound, 2i, which preferentially inhibits CDK2, CDK5, and aurora A was identified. Both biochemical and cellular assays indicated that treatment with compound 2i caused the downregulation of cyclins A and B, the dephosphorylation of histone H3 at Ser10, and the induction of mitochondrial apoptosis in the HCT-116 colon cancer cell line. It also reduced migration as well as tube and lamellipodia formation in human endothelial cells. The kinase inhibitory profile of compound 2i suggests that its anti-angiogenic activity is linked to CDK5 inhibition. This dual mode of action involving apoptosis induction in cancer ce
Název v anglickém jazyce
Characterization of a Pyrazolo[4,3-d]pyrimidine Inhibitor of Cyclin-dependent Kinases 2 and 5 and Aurora A With Pro-Apoptotic and Anti-Angiogenic Activity In Vitro
Popis výsledku anglicky
Selective inhibitors of kinases that regulate the cell cycle, such as cyclin-dependent kinases (CDKs) and aurora kinases, could potentially become powerful tools for the treatment of cancer. We prepared and studied a series of 3,5,7-trisubstituted pyrazolo[4,3-d]pyrimidines, a new CDK inhibitor scaffold, to assess their CDK2 inhibitory and antiproliferative activities. A new compound, 2i, which preferentially inhibits CDK2, CDK5, and aurora A was identified. Both biochemical and cellular assays indicated that treatment with compound 2i caused the downregulation of cyclins A and B, the dephosphorylation of histone H3 at Ser10, and the induction of mitochondrial apoptosis in the HCT-116 colon cancer cell line. It also reduced migration as well as tube and lamellipodia formation in human endothelial cells. The kinase inhibitory profile of compound 2i suggests that its anti-angiogenic activity is linked to CDK5 inhibition. This dual mode of action involving apoptosis induction in cancer ce
Klasifikace
Druh
J<sub>x</sub> - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)
CEP obor
CE - Biochemie
OECD FORD obor
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Návaznosti výsledku
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)<br>S - Specificky vyzkum na vysokych skolach
Ostatní
Rok uplatnění
2015
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Chemical Biology and Drug Design (Print)
ISSN
1747-0277
e-ISSN
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Svazek periodika
86
Číslo periodika v rámci svazku
6
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
13
Strana od-do
1528-1540
Kód UT WoS článku
000367376800022
EID výsledku v databázi Scopus
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