IRIS PubliCatt
PubliCatt è il repository istituzionale ad accesso aperto dell'Università Cattolica del Sacro Cuore, dove gli utenti autorizzati afferenti all'Ateneo provvedono direttamente e autonomamente a depositare e a rendere visibili le proprie pubblicazioni, inserendo i dati descrittivi del documento stesso ("metadati", quali il titolo, autore, abstract, etc.) e, laddove possibile, il testo della pubblicazione stessa (full-text).
PubliCatt utilizza la piattaforma IRIS (Institutional Research Information System) sviluppata da CINECA.
EnglishOverexpression of P-glycoprotein (P-gp) and other ATP-binding cassette (ABC) transporters in multidrug resistant (MDR) cancer cells is responsible for the reduction of intracellular drug accumulation, thus decreasing the efficacy of chemotherapeutics. P-gp is also found at endothelial cells' membrane of the blood-brain barrier, where it limits drug delivery to central nervous system (CNS) tumors. We have previously developed a set of pyrazolo[3,4-d]pyrimidines and their prodrugs as novel Src tyrosine kinase inhibitors (TKIs), showing a significant activity against CNS tumors in in vivo. Here we investigated the interaction of the most promising pair of drug/prodrug with P-gp at the cellular level. The tested compounds were found to increase the intracellular accumulation of Rho 123, and to enhance the efficacy of paclitaxel in P-gp overexpressing cells. Encouraging pharmacokinetics properties and tolerability in vivo were also observed. Our findings revealed a novel role of pyrazolo[3,4-d]pyrimidines which may be useful for developing a new effective therapy in MDR cancer treatment, particularly against glioblastoma.
Fallacara, A. L., Zamperini, C., Podolski-renić, A., Dinić, J., Stanković, T., Stepanović, M., Mancini, A., Rango, E., Iovenitti, G., Molinari, A., Bugli, F., Sanguinetti, M., Torelli, R., Martini, M., Maccari, L., Valoti, M., Dreassi, E., Botta, M., Pešić, M., Schenone, S., A New Strategy for Glioblastoma Treatment: In Vitro and In Vivo Preclinical Characterization of Si306, a Pyrazolo[3,4-d]Pyrimidine Dual Src/P-Glycoprotein Inhibitor, <<CANCERS>>, 2019; 11 (6): E848-N/A. [doi:10.3390/cancers11060848] [http://hdl.handle.net/10807/140205]
| Autori: | ||
| Titolo: | A New Strategy for Glioblastoma Treatment: In Vitro and In Vivo Preclinical Characterization of Si306, a Pyrazolo[3,4-d]Pyrimidine Dual Src/P-Glycoprotein Inhibitor | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.3390/cancers11060848 | |
| Data di pubblicazione: | 2019 | |
| Abstract: | Overexpression of P-glycoprotein (P-gp) and other ATP-binding cassette (ABC) transporters in multidrug resistant (MDR) cancer cells is responsible for the reduction of intracellular drug accumulation, thus decreasing the efficacy of chemotherapeutics. P-gp is also found at endothelial cells' membrane of the blood-brain barrier, where it limits drug delivery to central nervous system (CNS) tumors. We have previously developed a set of pyrazolo[3,4-d]pyrimidines and their prodrugs as novel Src tyrosine kinase inhibitors (TKIs), showing a significant activity against CNS tumors in in vivo. Here we investigated the interaction of the most promising pair of drug/prodrug with P-gp at the cellular level. The tested compounds were found to increase the intracellular accumulation of Rho 123, and to enhance the efficacy of paclitaxel in P-gp overexpressing cells. Encouraging pharmacokinetics properties and tolerability in vivo were also observed. Our findings revealed a novel role of pyrazolo[3,4-d]pyrimidines which may be useful for developing a new effective therapy in MDR cancer treatment, particularly against glioblastoma. | |
| Lingua: | Inglese | |
| Rivista: | ||
| Citazione: | Fallacara, A. L., Zamperini, C., Podolski-renić, A., Dinić, J., Stanković, T., Stepanović, M., Mancini, A., Rango, E., Iovenitti, G., Molinari, A., Bugli, F., Sanguinetti, M., Torelli, R., Martini, M., Maccari, L., Valoti, M., Dreassi, E., Botta, M., Pešić, M., Schenone, S., A New Strategy for Glioblastoma Treatment: In Vitro and In Vivo Preclinical Characterization of Si306, a Pyrazolo[3,4-d]Pyrimidine Dual Src/P-Glycoprotein Inhibitor, <<CANCERS>>, 2019; 11 (6): E848-N/A. [doi:10.3390/cancers11060848] [http://hdl.handle.net/10807/140205] | |
| Appare nelle tipologie: | Articolo in rivista, Nota a sentenza |
File in questo prodotto:
| File | Descrizione | Tipologia | Note | Licenza | |
|---|---|---|---|---|---|
| cancers-11-00848 (1).pdf | Versione Editoriale (PDF) | Nessuna Nota |  | Open Access Visualizza/Apri |
Copyright © 2022