TY  - JOUR
AU  - Fallacara, Ana Lucia
AU  - Zamperini, Claudio
AU  - Podolski-Renić, Ana
AU  - Dinić, Jelena
AU  - Stanković, Tijana
AU  - Nešović, Marija
AU  - Mancini, Arianna
AU  - Rango, Enrico
AU  - Iovenitti, Giulia
AU  - Molinari, Alessio
AU  - Bugli, Francesca
AU  - Sanguinetti, Maurizio
AU  - Torelli, Riccardo
AU  - Martini, Maurizio
AU  - Maccari, Laura
AU  - Valoti, Massimo
AU  - Dreassi, Elena
AU  - Botta, Maurizio
AU  - Pešić, Milica
AU  - Schenone, Silvia
PY  - 2019
UR  - https://www.mdpi.com/2072-6694/11/6/848
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3379
AB  - 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.
T2  - Cancers
T1  - 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
IS  - 6
VL  - 11
DO  - 10.3390/cancers11060848
SP  - 848
ER  - 

@article{
author = "Fallacara, Ana Lucia and Zamperini, Claudio and Podolski-Renić, Ana and Dinić, Jelena and Stanković, Tijana and Nešović, Marija and Mancini, Arianna and Rango, Enrico and Iovenitti, Giulia and Molinari, Alessio and Bugli, Francesca and Sanguinetti, Maurizio and Torelli, Riccardo and Martini, Maurizio and Maccari, Laura and Valoti, Massimo and Dreassi, Elena and Botta, Maurizio and Pešić, Milica and Schenone, Silvia",
year = "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.",
journal = "Cancers",
title = "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",
number = "6",
volume = "11",
doi = "10.3390/cancers11060848",
pages = "848"
}

Fallacara, A. L., Zamperini, C., Podolski-Renić, A., Dinić, J., Stanković, T., Nešović, 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.. (2019). 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. in Cancers, 11(6), 848.
https://doi.org/10.3390/cancers11060848

Fallacara AL, Zamperini C, Podolski-Renić A, Dinić J, Stanković T, Nešović 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. in Cancers. 2019;11(6):848.
doi:10.3390/cancers11060848 .

Fallacara, Ana Lucia, Zamperini, Claudio, Podolski-Renić, Ana, Dinić, Jelena, Stanković, Tijana, Nešović, Marija, Mancini, Arianna, Rango, Enrico, Iovenitti, Giulia, Molinari, Alessio, Bugli, Francesca, Sanguinetti, Maurizio, Torelli, Riccardo, Martini, Maurizio, Maccari, Laura, Valoti, Massimo, Dreassi, Elena, Botta, Maurizio, Pešić, Milica, Schenone, Silvia, "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" in Cancers, 11, no. 6 (2019):848,
https://doi.org/10.3390/cancers11060848 . .