TY  - JOUR
AU  - Jovanović Stojanov, Sofija
AU  - Stepanović, Ana
AU  - Ljujić, Mila
AU  - Lupšić, Ema
AU  - Schenone, Silvia
AU  - Pešić, Milica
AU  - Dinić, Jelena
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5043
AB  - Drug resistance presents a major obstacle to the successful treatment of glioblastoma. Autophagy plays a key role in drug resistance, particularly in relation to targeted therapy, which has prompted the use of autophagy inhibitors to increase the effectiveness of targeted therapeutics. The ability of two Src tyrosine kinase inhibitors, Si306 and its prodrug pro-Si306, to induce autophagy was evaluated in the human glioblastoma cell line U87 and its multidrug-resistant counterpart U87-TxR. Autophagy markers were assessed by flow cytometry, microscopy, and Western blot, and induction of autophagy by these compounds was demonstrated after 3 h as well as 48 h. The effects of Si306 and pro-Si306 on cell proliferation and cell death were examined in the presence or absence of autophagy inhibition by bafilomycin A1. Combined treatments of Si306 and pro-Si306 with bafilomycin A1 were synergistic in nature, and the inhibition of autophagy sensitized glioblastoma cells to Src tyrosine kinase inhibitors. Si306 and pro-Si306 more strongly inhibited cell proliferation and triggered necrosis in combination with bafilomycin A1. Our findings suggest that modulation of Si306- and pro-Si306-induced autophagy can be used to enhance the anticancer effects of these Src tyrosine kinase inhibitors and overcome the drug-resistant phenotype in glioblastoma cells.
PB  - Basel : MDPI
T2  - Life
T1  - Autophagy Inhibition Enhances Anti-Glioblastoma Effects of Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors
IS  - 10
VL  - 12
DO  - 10.3390/life12101503
SP  - 1503
ER  - 

@article{
author = "Jovanović Stojanov, Sofija and Stepanović, Ana and Ljujić, Mila and Lupšić, Ema and Schenone, Silvia and Pešić, Milica and Dinić, Jelena",
year = "2022",
abstract = "Drug resistance presents a major obstacle to the successful treatment of glioblastoma. Autophagy plays a key role in drug resistance, particularly in relation to targeted therapy, which has prompted the use of autophagy inhibitors to increase the effectiveness of targeted therapeutics. The ability of two Src tyrosine kinase inhibitors, Si306 and its prodrug pro-Si306, to induce autophagy was evaluated in the human glioblastoma cell line U87 and its multidrug-resistant counterpart U87-TxR. Autophagy markers were assessed by flow cytometry, microscopy, and Western blot, and induction of autophagy by these compounds was demonstrated after 3 h as well as 48 h. The effects of Si306 and pro-Si306 on cell proliferation and cell death were examined in the presence or absence of autophagy inhibition by bafilomycin A1. Combined treatments of Si306 and pro-Si306 with bafilomycin A1 were synergistic in nature, and the inhibition of autophagy sensitized glioblastoma cells to Src tyrosine kinase inhibitors. Si306 and pro-Si306 more strongly inhibited cell proliferation and triggered necrosis in combination with bafilomycin A1. Our findings suggest that modulation of Si306- and pro-Si306-induced autophagy can be used to enhance the anticancer effects of these Src tyrosine kinase inhibitors and overcome the drug-resistant phenotype in glioblastoma cells.",
publisher = "Basel : MDPI",
journal = "Life",
title = "Autophagy Inhibition Enhances Anti-Glioblastoma Effects of Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors",
number = "10",
volume = "12",
doi = "10.3390/life12101503",
pages = "1503"
}

Jovanović Stojanov, S., Stepanović, A., Ljujić, M., Lupšić, E., Schenone, S., Pešić, M.,& Dinić, J.. (2022). Autophagy Inhibition Enhances Anti-Glioblastoma Effects of Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors. in Life
Basel : MDPI., 12(10), 1503.
https://doi.org/10.3390/life12101503

Jovanović Stojanov S, Stepanović A, Ljujić M, Lupšić E, Schenone S, Pešić M, Dinić J. Autophagy Inhibition Enhances Anti-Glioblastoma Effects of Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors. in Life. 2022;12(10):1503.
doi:10.3390/life12101503 .

Jovanović Stojanov, Sofija, Stepanović, Ana, Ljujić, Mila, Lupšić, Ema, Schenone, Silvia, Pešić, Milica, Dinić, Jelena, "Autophagy Inhibition Enhances Anti-Glioblastoma Effects of Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors" in Life, 12, no. 10 (2022):1503,
https://doi.org/10.3390/life12101503 . .

TY  - CONF
AU  - Jovanović Stojanov, Sofija
AU  - Stepanović, Ana
AU  - Ljujić, Mila
AU  - Lupšić, Ema
AU  - Podolski-Renić, Ana
AU  - Dragoj, Miodrag
AU  - Jovanović, Mirna
AU  - Schenone, Silvia
AU  - Pešić, Milica
AU  - Dinić, Jelena
PY  - 2022
UR  - http://nwm.covr.be/EACR2022abstracts/data/HtmlApp/main.html#
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5425
AB  - Introduction:
Glioblastoma (GBM) is among the most frequent and aggressive brain tumors characterized by
infiltrating nature, high proliferation, and resistance to chemotherapy and radiation. GBM exhibit high
expression of Src tyrosine kinase which regulates proliferation, survival, and invasiveness of tumor
cells, making Src a potential target for GBM therapy. Numerous Src family kinase inhibitors (SFKI)
were reported to induce autophagy, thus protecting cells from undergoing cell death. However,
inhibition of autophagy was shown to sensitize cells to SFKI in several cancer types.
Material and Methods:
Human GBM cell line U87 and its multidrug-resistant (MDR) counterpart U87-TxR were transfected
with RFP-LC3, an autophagy marker. The ability of two SFKIs, pyrazolo[3,4-d]pyrimidines Si306 and
its prodrug pro-si306, to induce autophagy in RFP-LC3-transfected GBM cells was evaluated by flow
cytometry and fluorescent microscopy. Cell viability was assessed by MTT assay. The autophagy
induction and autophagic flux were evaluated by Acridine orange assay, immunocytochemistry and
immunoblotting. Cell proliferation rate was analyzed by CFSE assay. Cell death was detected by
Annexin/Propidium Iodide assay. PARP-1 cleavage was assessed by immunoblotting.
Results and Discussions:
SFKI treatment resulted in degradation of RFP-LC3 after 3 h treatment as well as in formation of
RFP-LC3 puncta in GBM cells demonstrating autophagy induction. The effect of SFKIs on autophagy
induction persisted after 48 h, as demonstrated by autophagy markers LC3 and p62. Inhibition of
autophagy by Bafilomycin A1 sensitized both U87 and U87-TxR cells to Si306 and its pro-drug after
48 h. The anti-proliferative effect of Si306 and pro-Si306 was additionally increased after autophagy
inhibition by Bafilomycin A1. Furthermore, while single SFKI treatments did not cause significant
cell death, combination treatments with autophagy inhibitor induced necrosis in U87 and U87-TxR
cells after 48 h. Detection of necrotic PARP-1 fragment further confirmed necrotic cell death.
Conclusion:
Taken together, these data suggest that autophagy induced by Si306 and pro-Si306 has a protective
role in GBM cells, and that autophagy modulation may be used to enhance the anticancer effects of
SFKIs. In addition, as the ability of the SFKIs to induce autophagy was not diminished by the
presence of the MDR phenotype makes these compounds promising for treatment of MDR cancers.
PB  - European Association for Cancer Research
C3  - Congress abstracts: Annual Congress of the European Association for Cancer Research EACR 2022: Innovative Cancer Service: Translating Biology to Medicine; 2022 Jun 20-23; Seville, Spain
T1  - Autophagy inhibition sensitises glioblastoma cells to Src family kinase inhibitors Si306 and its prodrug
SP  - P1-135
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5425
ER  - 

@conference{
author = "Jovanović Stojanov, Sofija and Stepanović, Ana and Ljujić, Mila and Lupšić, Ema and Podolski-Renić, Ana and Dragoj, Miodrag and Jovanović, Mirna and Schenone, Silvia and Pešić, Milica and Dinić, Jelena",
year = "2022",
abstract = "Introduction:
Glioblastoma (GBM) is among the most frequent and aggressive brain tumors characterized by
infiltrating nature, high proliferation, and resistance to chemotherapy and radiation. GBM exhibit high
expression of Src tyrosine kinase which regulates proliferation, survival, and invasiveness of tumor
cells, making Src a potential target for GBM therapy. Numerous Src family kinase inhibitors (SFKI)
were reported to induce autophagy, thus protecting cells from undergoing cell death. However,
inhibition of autophagy was shown to sensitize cells to SFKI in several cancer types.
Material and Methods:
Human GBM cell line U87 and its multidrug-resistant (MDR) counterpart U87-TxR were transfected
with RFP-LC3, an autophagy marker. The ability of two SFKIs, pyrazolo[3,4-d]pyrimidines Si306 and
its prodrug pro-si306, to induce autophagy in RFP-LC3-transfected GBM cells was evaluated by flow
cytometry and fluorescent microscopy. Cell viability was assessed by MTT assay. The autophagy
induction and autophagic flux were evaluated by Acridine orange assay, immunocytochemistry and
immunoblotting. Cell proliferation rate was analyzed by CFSE assay. Cell death was detected by
Annexin/Propidium Iodide assay. PARP-1 cleavage was assessed by immunoblotting.
Results and Discussions:
SFKI treatment resulted in degradation of RFP-LC3 after 3 h treatment as well as in formation of
RFP-LC3 puncta in GBM cells demonstrating autophagy induction. The effect of SFKIs on autophagy
induction persisted after 48 h, as demonstrated by autophagy markers LC3 and p62. Inhibition of
autophagy by Bafilomycin A1 sensitized both U87 and U87-TxR cells to Si306 and its pro-drug after
48 h. The anti-proliferative effect of Si306 and pro-Si306 was additionally increased after autophagy
inhibition by Bafilomycin A1. Furthermore, while single SFKI treatments did not cause significant
cell death, combination treatments with autophagy inhibitor induced necrosis in U87 and U87-TxR
cells after 48 h. Detection of necrotic PARP-1 fragment further confirmed necrotic cell death.
Conclusion:
Taken together, these data suggest that autophagy induced by Si306 and pro-Si306 has a protective
role in GBM cells, and that autophagy modulation may be used to enhance the anticancer effects of
SFKIs. In addition, as the ability of the SFKIs to induce autophagy was not diminished by the
presence of the MDR phenotype makes these compounds promising for treatment of MDR cancers.",
publisher = "European Association for Cancer Research",
journal = "Congress abstracts: Annual Congress of the European Association for Cancer Research EACR 2022: Innovative Cancer Service: Translating Biology to Medicine; 2022 Jun 20-23; Seville, Spain",
title = "Autophagy inhibition sensitises glioblastoma cells to Src family kinase inhibitors Si306 and its prodrug",
pages = "P1-135",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5425"
}

Jovanović Stojanov, S., Stepanović, A., Ljujić, M., Lupšić, E., Podolski-Renić, A., Dragoj, M., Jovanović, M., Schenone, S., Pešić, M.,& Dinić, J.. (2022). Autophagy inhibition sensitises glioblastoma cells to Src family kinase inhibitors Si306 and its prodrug. in Congress abstracts: Annual Congress of the European Association for Cancer Research EACR 2022: Innovative Cancer Service: Translating Biology to Medicine; 2022 Jun 20-23; Seville, Spain
European Association for Cancer Research., P1-135.
https://hdl.handle.net/21.15107/rcub_ibiss_5425

Jovanović Stojanov S, Stepanović A, Ljujić M, Lupšić E, Podolski-Renić A, Dragoj M, Jovanović M, Schenone S, Pešić M, Dinić J. Autophagy inhibition sensitises glioblastoma cells to Src family kinase inhibitors Si306 and its prodrug. in Congress abstracts: Annual Congress of the European Association for Cancer Research EACR 2022: Innovative Cancer Service: Translating Biology to Medicine; 2022 Jun 20-23; Seville, Spain. 2022;:P1-135.
https://hdl.handle.net/21.15107/rcub_ibiss_5425 .

Jovanović Stojanov, Sofija, Stepanović, Ana, Ljujić, Mila, Lupšić, Ema, Podolski-Renić, Ana, Dragoj, Miodrag, Jovanović, Mirna, Schenone, Silvia, Pešić, Milica, Dinić, Jelena, "Autophagy inhibition sensitises glioblastoma cells to Src family kinase inhibitors Si306 and its prodrug" in Congress abstracts: Annual Congress of the European Association for Cancer Research EACR 2022: Innovative Cancer Service: Translating Biology to Medicine; 2022 Jun 20-23; Seville, Spain (2022):P1-135,
https://hdl.handle.net/21.15107/rcub_ibiss_5425 .

TY  - CONF
AU  - Stepanović, Ana
AU  - Podolski-Renić, Ana
AU  - Jovanović Stojanov, Sofija
AU  - Nešović, Marija
AU  - Dragoj, Miodrag
AU  - Jovanović, Mirna
AU  - Nikolić, Igor
AU  - Tasić, Goran
AU  - Schenone, Silvia
AU  - Pešić, Milica
AU  - Dinić, Jelena
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4801
AB  - Glioblastoma is the most frequent and aggressive brain tumor in adults. The main characteristics of glioblastoma include high proliferation rate, infiltrating nature, and resistance to chemotherapy and radiation. Glioblastoma cells highly express Src tyrosine kinase which has a key role in regulating survival, proliferation, angiogenesis and invasiveness of tumor cells. This tyrosine kinase is also an important regulator of reactive oxygen species production and cellular homeostasis. Anticancer properties of two pyrazolo[3,4-d]pyrimidine derivatives and Src tyrosine kinase inhibitors, Si306 and its prodrug pro-Si306, were investigated in human glioblastoma cell line U87, its multidrug-resistant (MDR) counterpart U87-TxR, and patient-derived glioblastoma cell culture. Si306 and pro-Si306 triggered reactive oxygen species and reactive nitrogen species production in sensitive and MDR glioblastoma cell lines and primary glioblastoma cells as evidenced by elevated levels of superoxide anion, hydrogen peroxide and peroxynitrite anion. Additionally, western blot analysis revealed elevated expression of superoxide dismutase 1, superoxide dismutase 2, and thioredoxin reductase 1 in glioblastoma cells after Si306 and pro-Si306 treatments. The levels of phosphorylated histone H2A.X increased in all glioblastoma cells after treatments with these inhibitors, demonstrating DNA damage. Both compounds also induced significant cell death in primary glioblastoma culture. In addition, the Src tyrosine kinase inhibitors prompted primary glioblastoma cells to enter senescence. The presence of the MDR phenotype did not reduce the activity of the compounds. Overall, the investigated pyrazolo[3,4-d]pyrimidines displayed significant anti-glioblastoma effects making them good candidates for further development as anticancer agents
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - Pyrazolo[3,4-d]pyrimidine derivatives, Si306 and pro-Si306, induce oxidative stress and cell death in patient-derived glioblastoma cells
DO  - 10.1016/j.freeradbiomed.2021.08.082
SP  - S75
ER  - 

@conference{
author = "Stepanović, Ana and Podolski-Renić, Ana and Jovanović Stojanov, Sofija and Nešović, Marija and Dragoj, Miodrag and Jovanović, Mirna and Nikolić, Igor and Tasić, Goran and Schenone, Silvia and Pešić, Milica and Dinić, Jelena",
year = "2021",
abstract = "Glioblastoma is the most frequent and aggressive brain tumor in adults. The main characteristics of glioblastoma include high proliferation rate, infiltrating nature, and resistance to chemotherapy and radiation. Glioblastoma cells highly express Src tyrosine kinase which has a key role in regulating survival, proliferation, angiogenesis and invasiveness of tumor cells. This tyrosine kinase is also an important regulator of reactive oxygen species production and cellular homeostasis. Anticancer properties of two pyrazolo[3,4-d]pyrimidine derivatives and Src tyrosine kinase inhibitors, Si306 and its prodrug pro-Si306, were investigated in human glioblastoma cell line U87, its multidrug-resistant (MDR) counterpart U87-TxR, and patient-derived glioblastoma cell culture. Si306 and pro-Si306 triggered reactive oxygen species and reactive nitrogen species production in sensitive and MDR glioblastoma cell lines and primary glioblastoma cells as evidenced by elevated levels of superoxide anion, hydrogen peroxide and peroxynitrite anion. Additionally, western blot analysis revealed elevated expression of superoxide dismutase 1, superoxide dismutase 2, and thioredoxin reductase 1 in glioblastoma cells after Si306 and pro-Si306 treatments. The levels of phosphorylated histone H2A.X increased in all glioblastoma cells after treatments with these inhibitors, demonstrating DNA damage. Both compounds also induced significant cell death in primary glioblastoma culture. In addition, the Src tyrosine kinase inhibitors prompted primary glioblastoma cells to enter senescence. The presence of the MDR phenotype did not reduce the activity of the compounds. Overall, the investigated pyrazolo[3,4-d]pyrimidines displayed significant anti-glioblastoma effects making them good candidates for further development as anticancer agents",
publisher = "Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "Pyrazolo[3,4-d]pyrimidine derivatives, Si306 and pro-Si306, induce oxidative stress and cell death in patient-derived glioblastoma cells",
doi = "10.1016/j.freeradbiomed.2021.08.082",
pages = "S75"
}

Stepanović, A., Podolski-Renić, A., Jovanović Stojanov, S., Nešović, M., Dragoj, M., Jovanović, M., Nikolić, I., Tasić, G., Schenone, S., Pešić, M.,& Dinić, J.. (2021). Pyrazolo[3,4-d]pyrimidine derivatives, Si306 and pro-Si306, induce oxidative stress and cell death in patient-derived glioblastoma cells. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier Inc.., S75.
https://doi.org/10.1016/j.freeradbiomed.2021.08.082

Stepanović A, Podolski-Renić A, Jovanović Stojanov S, Nešović M, Dragoj M, Jovanović M, Nikolić I, Tasić G, Schenone S, Pešić M, Dinić J. Pyrazolo[3,4-d]pyrimidine derivatives, Si306 and pro-Si306, induce oxidative stress and cell death in patient-derived glioblastoma cells. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:S75.
doi:10.1016/j.freeradbiomed.2021.08.082 .

Stepanović, Ana, Podolski-Renić, Ana, Jovanović Stojanov, Sofija, Nešović, Marija, Dragoj, Miodrag, Jovanović, Mirna, Nikolić, Igor, Tasić, Goran, Schenone, Silvia, Pešić, Milica, Dinić, Jelena, "Pyrazolo[3,4-d]pyrimidine derivatives, Si306 and pro-Si306, induce oxidative stress and cell death in patient-derived glioblastoma cells" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):S75,
https://doi.org/10.1016/j.freeradbiomed.2021.08.082 . .

TY  - JOUR
AU  - Stepanović, Ana
AU  - Jovanović Stojanov, Sofija
AU  - Podolski-Renić, Ana
AU  - Nešović, Marija
AU  - Dragoj, Miodrag
AU  - Nikolić, Igor
AU  - Tasić, Goran
AU  - Schenone, Silvia
AU  - Pešić, Milica
AU  - Dinić, Jelena
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4258
AB  - Background: Glioblastoma (GBM) highly expresses Src tyrosine kinase involved in survival, proliferation, angiogenesis and invasiveness of tumor cells. Src activation also reduces reactive oxygen species (ROS) generation, whereas Src inhibitors are able to increase cellular ROS levels. Methods: Pro-oxidative effects of two pyrazolo[3,4-d]pyrimidine derivatives—Src tyrosine kinase inhibitors, Si306 and its prodrug pro-Si306—were investigated in human GBM cells U87 and patient-derived GBM-6. ROS production and changes in mitochondrial membrane potential were assessed by flow cytometry. The expression levels of superoxide dismutase 1 (SOD1) and 2 (SOD2) were studied by Western blot. DNA damage, cell death induction and senescence were also examined in GBM-6 cells. Results: Si306 and pro-Si306 more prominently triggered ROS production and expression of antioxidant enzymes in primary GBM cells. These effects were followed by mitochondrial membrane potential disruption, double-strand DNA breaks and senescence that eventually led to necrosis. Conclusion: Src kinase inhibitors, Si306 and pro-Si306, showed significant pro-oxidative potential in patient-derived GBM cells. This feature contributes to the already demonstrated anti-glioblastoma properties of these compounds in vitro and in vivo and encourages clinical investigations.
PB  - Basel : MDPI
T2  - Brain Sciences
T1  - Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors Induce Oxidative Stress in Patient-Derived Glioblastoma Cells
IS  - 7
VL  - 11
DO  - 10.3390/brainsci11070884
SP  - 884
ER  - 

@article{
author = "Stepanović, Ana and Jovanović Stojanov, Sofija and Podolski-Renić, Ana and Nešović, Marija and Dragoj, Miodrag and Nikolić, Igor and Tasić, Goran and Schenone, Silvia and Pešić, Milica and Dinić, Jelena",
year = "2021",
abstract = "Background: Glioblastoma (GBM) highly expresses Src tyrosine kinase involved in survival, proliferation, angiogenesis and invasiveness of tumor cells. Src activation also reduces reactive oxygen species (ROS) generation, whereas Src inhibitors are able to increase cellular ROS levels. Methods: Pro-oxidative effects of two pyrazolo[3,4-d]pyrimidine derivatives—Src tyrosine kinase inhibitors, Si306 and its prodrug pro-Si306—were investigated in human GBM cells U87 and patient-derived GBM-6. ROS production and changes in mitochondrial membrane potential were assessed by flow cytometry. The expression levels of superoxide dismutase 1 (SOD1) and 2 (SOD2) were studied by Western blot. DNA damage, cell death induction and senescence were also examined in GBM-6 cells. Results: Si306 and pro-Si306 more prominently triggered ROS production and expression of antioxidant enzymes in primary GBM cells. These effects were followed by mitochondrial membrane potential disruption, double-strand DNA breaks and senescence that eventually led to necrosis. Conclusion: Src kinase inhibitors, Si306 and pro-Si306, showed significant pro-oxidative potential in patient-derived GBM cells. This feature contributes to the already demonstrated anti-glioblastoma properties of these compounds in vitro and in vivo and encourages clinical investigations.",
publisher = "Basel : MDPI",
journal = "Brain Sciences",
title = "Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors Induce Oxidative Stress in Patient-Derived Glioblastoma Cells",
number = "7",
volume = "11",
doi = "10.3390/brainsci11070884",
pages = "884"
}

Stepanović, A., Jovanović Stojanov, S., Podolski-Renić, A., Nešović, M., Dragoj, M., Nikolić, I., Tasić, G., Schenone, S., Pešić, M.,& Dinić, J.. (2021). Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors Induce Oxidative Stress in Patient-Derived Glioblastoma Cells. in Brain Sciences
Basel : MDPI., 11(7), 884.
https://doi.org/10.3390/brainsci11070884

Stepanović A, Jovanović Stojanov S, Podolski-Renić A, Nešović M, Dragoj M, Nikolić I, Tasić G, Schenone S, Pešić M, Dinić J. Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors Induce Oxidative Stress in Patient-Derived Glioblastoma Cells. in Brain Sciences. 2021;11(7):884.
doi:10.3390/brainsci11070884 .

Stepanović, Ana, Jovanović Stojanov, Sofija, Podolski-Renić, Ana, Nešović, Marija, Dragoj, Miodrag, Nikolić, Igor, Tasić, Goran, Schenone, Silvia, Pešić, Milica, Dinić, Jelena, "Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors Induce Oxidative Stress in Patient-Derived Glioblastoma Cells" in Brain Sciences, 11, no. 7 (2021):884,
https://doi.org/10.3390/brainsci11070884 . .

TY  - JOUR
AU  - Podolski-Renić, Ana
AU  - Dinić, Jelena
AU  - Stanković, Tijana
AU  - Tsakovska, Ivanka
AU  - Pajeva, Ilza
AU  - Tuccinardi, Tiziano
AU  - Botta, Lorenzo
AU  - Schenone, Silvia
AU  - Pešić, Milica
PY  - 2021
UR  - https://www.mdpi.com/2072-6694/13/21/5308
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4631
AB  - Tyrosine kinase inhibitors (TKIs) often interact with the multidrug resistant (MDR) phenotype of cancer cells. In some cases, TKIs increase the susceptibility of MDR cancer cells to chemotherapy. As the overexpression of membrane transporter P‐glycoprotein (P‐gp) is the most com-mon alteration in MDR cancer cells, we investigated the effects of TKI pyrazolo[3,4‐d]pyrimidines on P‐gp inhibition in two cellular models comprising sensitive and corresponding MDR cancer cells (human non‐small cell lung carcinoma and colorectal adenocarcinoma). Tested TKIs showed collateral sensitivity by inducing stronger inhibition of MDR cancer cell line viability. Moreover, TKIs directly interacted with P‐gp and inhibited its ATPase activity. Their potential P‐gp binding site was proposed by molecular docking simulations. TKIs reversed resistance to doxorubicin and paclitaxel in a concentration‐dependent manner. The expression studies excluded the indirect effect of TKIs on P‐gp through regulation of its expression. A kinetics study showed that TKIs decreased P‐gp activity and this effect was sustained for seven days in both MDR models. Therefore, pyrazolo[3,4‐d]pyrimidines with potential for reversing P‐gp‐mediated MDR even in prolonged treatments can be considered a new therapeutic strategy for overcoming cancer MDR.
PB  - Basel: MDPI
T2  - Cancers
T1  - New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors
IS  - 21
VL  - 13
DO  - 10.3390/cancers13215308
SP  - 5308
ER  - 

@article{
author = "Podolski-Renić, Ana and Dinić, Jelena and Stanković, Tijana and Tsakovska, Ivanka and Pajeva, Ilza and Tuccinardi, Tiziano and Botta, Lorenzo and Schenone, Silvia and Pešić, Milica",
year = "2021",
abstract = "Tyrosine kinase inhibitors (TKIs) often interact with the multidrug resistant (MDR) phenotype of cancer cells. In some cases, TKIs increase the susceptibility of MDR cancer cells to chemotherapy. As the overexpression of membrane transporter P‐glycoprotein (P‐gp) is the most com-mon alteration in MDR cancer cells, we investigated the effects of TKI pyrazolo[3,4‐d]pyrimidines on P‐gp inhibition in two cellular models comprising sensitive and corresponding MDR cancer cells (human non‐small cell lung carcinoma and colorectal adenocarcinoma). Tested TKIs showed collateral sensitivity by inducing stronger inhibition of MDR cancer cell line viability. Moreover, TKIs directly interacted with P‐gp and inhibited its ATPase activity. Their potential P‐gp binding site was proposed by molecular docking simulations. TKIs reversed resistance to doxorubicin and paclitaxel in a concentration‐dependent manner. The expression studies excluded the indirect effect of TKIs on P‐gp through regulation of its expression. A kinetics study showed that TKIs decreased P‐gp activity and this effect was sustained for seven days in both MDR models. Therefore, pyrazolo[3,4‐d]pyrimidines with potential for reversing P‐gp‐mediated MDR even in prolonged treatments can be considered a new therapeutic strategy for overcoming cancer MDR.",
publisher = "Basel: MDPI",
journal = "Cancers",
title = "New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors",
number = "21",
volume = "13",
doi = "10.3390/cancers13215308",
pages = "5308"
}

Podolski-Renić, A., Dinić, J., Stanković, T., Tsakovska, I., Pajeva, I., Tuccinardi, T., Botta, L., Schenone, S.,& Pešić, M.. (2021). New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors. in Cancers
Basel: MDPI., 13(21), 5308.
https://doi.org/10.3390/cancers13215308

Podolski-Renić A, Dinić J, Stanković T, Tsakovska I, Pajeva I, Tuccinardi T, Botta L, Schenone S, Pešić M. New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors. in Cancers. 2021;13(21):5308.
doi:10.3390/cancers13215308 .

Podolski-Renić, Ana, Dinić, Jelena, Stanković, Tijana, Tsakovska, Ivanka, Pajeva, Ilza, Tuccinardi, Tiziano, Botta, Lorenzo, Schenone, Silvia, Pešić, Milica, "New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors" in Cancers, 13, no. 21 (2021):5308,
https://doi.org/10.3390/cancers13215308 . .

TY  - JOUR
AU  - Nešović, Marija
AU  - Divac Rankov, Aleksandra
AU  - Podolski-Renić, Ana
AU  - Nikolić, Igor
AU  - Tasić, Goran
AU  - Mancini, Arianna
AU  - Schenone, Silvia
AU  - Pešić, Milica
AU  - Dinić, Jelena
PY  - 2020
UR  - https://www.mdpi.com/2072-6694/12/6/1570
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3818
AB  - Glioblastoma (GBM), as the most aggressive brain tumor, displays a high expression of Src tyrosine kinase, which is involved in the survival, migration, and invasiveness of tumor cells. Thus, Src emerged as a potential target for GBM therapy. The effects of Src inhibitors pyrazolo[3,4-d]pyrimidines, Si306 and its prodrug pro-Si306 were investigated in human GBM cell lines (U87 and U87-TxR) and three primary GBM cell cultures. Primary GBM cells were more resistant to Si306 and pro-Si306 according to the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. However, the ability of all GBM cells to degrade the extracellular matrix was considerably compromised after Si306 and pro-Si306 applications. Besides reducing the phosphorylation of Src and its downstream signaling pathway components, both compounds decreased the phosphorylated form of focal adhesion kinase (FAK) and epidermal growth factor receptor (EGFR) expression, showing the potential to suppress the aggressiveness of GBM. In vivo, Si306 and pro-Si306 displayed an anti-invasive effect against U87 xenografts in the zebrafish embryo model. Considering that Si306 and pro-Si306 are able to cross the blood-brain barrier and suppress the spread of GBM cells, we anticipate their clinical testing in the near future. Moreover, the prodrug showed similar efficacy to the drug, implying the rationality of its use in clinical settings.
PB  - Basel : MDPI
T2  - Cancers (Basel)
T1  - Src Inhibitors Pyrazolo[3,4-d]pyrimidines, Si306 and Pro-Si306, Inhibit Focal Adhesion Kinase and Suppress Human Glioblastoma Invasion In Vitro and In Vivo
IS  - 6
VL  - 12
DO  - 10.3390/cancers12061570
SP  - 1570
ER  - 

@article{
author = "Nešović, Marija and Divac Rankov, Aleksandra and Podolski-Renić, Ana and Nikolić, Igor and Tasić, Goran and Mancini, Arianna and Schenone, Silvia and Pešić, Milica and Dinić, Jelena",
year = "2020",
abstract = "Glioblastoma (GBM), as the most aggressive brain tumor, displays a high expression of Src tyrosine kinase, which is involved in the survival, migration, and invasiveness of tumor cells. Thus, Src emerged as a potential target for GBM therapy. The effects of Src inhibitors pyrazolo[3,4-d]pyrimidines, Si306 and its prodrug pro-Si306 were investigated in human GBM cell lines (U87 and U87-TxR) and three primary GBM cell cultures. Primary GBM cells were more resistant to Si306 and pro-Si306 according to the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. However, the ability of all GBM cells to degrade the extracellular matrix was considerably compromised after Si306 and pro-Si306 applications. Besides reducing the phosphorylation of Src and its downstream signaling pathway components, both compounds decreased the phosphorylated form of focal adhesion kinase (FAK) and epidermal growth factor receptor (EGFR) expression, showing the potential to suppress the aggressiveness of GBM. In vivo, Si306 and pro-Si306 displayed an anti-invasive effect against U87 xenografts in the zebrafish embryo model. Considering that Si306 and pro-Si306 are able to cross the blood-brain barrier and suppress the spread of GBM cells, we anticipate their clinical testing in the near future. Moreover, the prodrug showed similar efficacy to the drug, implying the rationality of its use in clinical settings.",
publisher = "Basel : MDPI",
journal = "Cancers (Basel)",
title = "Src Inhibitors Pyrazolo[3,4-d]pyrimidines, Si306 and Pro-Si306, Inhibit Focal Adhesion Kinase and Suppress Human Glioblastoma Invasion In Vitro and In Vivo",
number = "6",
volume = "12",
doi = "10.3390/cancers12061570",
pages = "1570"
}

Nešović, M., Divac Rankov, A., Podolski-Renić, A., Nikolić, I., Tasić, G., Mancini, A., Schenone, S., Pešić, M.,& Dinić, J.. (2020). Src Inhibitors Pyrazolo[3,4-d]pyrimidines, Si306 and Pro-Si306, Inhibit Focal Adhesion Kinase and Suppress Human Glioblastoma Invasion In Vitro and In Vivo. in Cancers (Basel)
Basel : MDPI., 12(6), 1570.
https://doi.org/10.3390/cancers12061570

Nešović M, Divac Rankov A, Podolski-Renić A, Nikolić I, Tasić G, Mancini A, Schenone S, Pešić M, Dinić J. Src Inhibitors Pyrazolo[3,4-d]pyrimidines, Si306 and Pro-Si306, Inhibit Focal Adhesion Kinase and Suppress Human Glioblastoma Invasion In Vitro and In Vivo. in Cancers (Basel). 2020;12(6):1570.
doi:10.3390/cancers12061570 .

Nešović, Marija, Divac Rankov, Aleksandra, Podolski-Renić, Ana, Nikolić, Igor, Tasić, Goran, Mancini, Arianna, Schenone, Silvia, Pešić, Milica, Dinić, Jelena, "Src Inhibitors Pyrazolo[3,4-d]pyrimidines, Si306 and Pro-Si306, Inhibit Focal Adhesion Kinase and Suppress Human Glioblastoma Invasion In Vitro and In Vivo" in Cancers (Basel), 12, no. 6 (2020):1570,
https://doi.org/10.3390/cancers12061570 . .

TY  - CONF
AU  - Nešović, Marija
AU  - Podolski-Renić, Ana
AU  - Stanković, Tijana
AU  - Divac Rankov, Aleksandra
AU  - Fallacara, Anna Lucia
AU  - Schenone, Silvia
AU  - Botta, Maurizio
AU  - Pešić, Milica
AU  - Dinić, Jelena
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6045
AB  - Glioblastoma multiforme (GBM) are the most frequent and aggressive (WHO grade IV) brain
tumors in adults. GBM have high expression of c-Src tyrosine kinase involved in survival,
migration and invasiveness of tumor cells. Thus, c-Src emerged as a potential target for GBM
therapy. Cytotoxicity of c-Src inhibitors pyrozolo[3,4-d]pyrimidines, Si306 and its prodrug pro-Si306,
was investigated in human GBM cell line U87 and its multidrug resistant (MDR) counterpart
U87-TxR by MTT assay. Anti-migratory and anti-invasive effects of Si306 and pro-Si306 were
assessed by wound healing, gelatin degradation and transwell invasion assays. The effect of cSrc inhibitors on P-glycoprotein (P-gp) activity in U87-TxR cells was analyzed by flow cytometry. Their ability to reverse paclitaxel resistance in MDR cells was also assessed. Zebrafish model was used to evaluate anti-invasive potential of pro-Si306 on U87 xenografts in vivo. Novel c-Src inhibitors were significantly more efficient in cell growth inhibition compared to the well-known tyrosine kinase inhibitor dasatinib. The efficacy of Si306 and pro-Si306 was not affected by the MDR phenotype.
Migratory potential of U87 and U87-TxR cells was significantly decreased by both inhibitors.
The ability of cells to degrade the matrix and invade through basement membrane was also
significantly impaired upon treatment with Si306 and its prodrug. Assessment of intracellular
accumulation of fluorescent P-gp substrate showed that both compounds inhibited P-gp activity
in U87-TxR cells. Si306 and pro-Si306 also enhanced the paclitaxel efficacy in resistant
glioblastoma. In vivo pro-Si306 showed anti-invasive effect against U87 xenografts in zebrafish
model. Considering their ability to suppress migration and invasion and overcome MDR, Si306 and proSi306 could be considered in GBM treatment alone or in combination with other
chemotherapeutics.
PB  - COST Action CM1407
C3  - COST Action CM1407: Challenging organic syntheses inspired by naturefrom natural products chemistry to drug discovery: Meeting dedicated to Early career Investigators; 2019 Feb 18-19; Brussels, Belgium
T1  - The potential of c-Src inhibitors Si306 and pro-Si306 for suppressing invasion and overcoming multidrug resistance in glioblastoma
SP  - 9
EP  - 9
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6045
ER  - 

@conference{
author = "Nešović, Marija and Podolski-Renić, Ana and Stanković, Tijana and Divac Rankov, Aleksandra and Fallacara, Anna Lucia and Schenone, Silvia and Botta, Maurizio and Pešić, Milica and Dinić, Jelena",
year = "2019",
abstract = "Glioblastoma multiforme (GBM) are the most frequent and aggressive (WHO grade IV) brain
tumors in adults. GBM have high expression of c-Src tyrosine kinase involved in survival,
migration and invasiveness of tumor cells. Thus, c-Src emerged as a potential target for GBM
therapy. Cytotoxicity of c-Src inhibitors pyrozolo[3,4-d]pyrimidines, Si306 and its prodrug pro-Si306,
was investigated in human GBM cell line U87 and its multidrug resistant (MDR) counterpart
U87-TxR by MTT assay. Anti-migratory and anti-invasive effects of Si306 and pro-Si306 were
assessed by wound healing, gelatin degradation and transwell invasion assays. The effect of cSrc inhibitors on P-glycoprotein (P-gp) activity in U87-TxR cells was analyzed by flow cytometry. Their ability to reverse paclitaxel resistance in MDR cells was also assessed. Zebrafish model was used to evaluate anti-invasive potential of pro-Si306 on U87 xenografts in vivo. Novel c-Src inhibitors were significantly more efficient in cell growth inhibition compared to the well-known tyrosine kinase inhibitor dasatinib. The efficacy of Si306 and pro-Si306 was not affected by the MDR phenotype.
Migratory potential of U87 and U87-TxR cells was significantly decreased by both inhibitors.
The ability of cells to degrade the matrix and invade through basement membrane was also
significantly impaired upon treatment with Si306 and its prodrug. Assessment of intracellular
accumulation of fluorescent P-gp substrate showed that both compounds inhibited P-gp activity
in U87-TxR cells. Si306 and pro-Si306 also enhanced the paclitaxel efficacy in resistant
glioblastoma. In vivo pro-Si306 showed anti-invasive effect against U87 xenografts in zebrafish
model. Considering their ability to suppress migration and invasion and overcome MDR, Si306 and proSi306 could be considered in GBM treatment alone or in combination with other
chemotherapeutics.",
publisher = "COST Action CM1407",
journal = "COST Action CM1407: Challenging organic syntheses inspired by naturefrom natural products chemistry to drug discovery: Meeting dedicated to Early career Investigators; 2019 Feb 18-19; Brussels, Belgium",
title = "The potential of c-Src inhibitors Si306 and pro-Si306 for suppressing invasion and overcoming multidrug resistance in glioblastoma",
pages = "9-9",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6045"
}

Nešović, M., Podolski-Renić, A., Stanković, T., Divac Rankov, A., Fallacara, A. L., Schenone, S., Botta, M., Pešić, M.,& Dinić, J.. (2019). The potential of c-Src inhibitors Si306 and pro-Si306 for suppressing invasion and overcoming multidrug resistance in glioblastoma. in COST Action CM1407: Challenging organic syntheses inspired by naturefrom natural products chemistry to drug discovery: Meeting dedicated to Early career Investigators; 2019 Feb 18-19; Brussels, Belgium
COST Action CM1407., 9-9.
https://hdl.handle.net/21.15107/rcub_ibiss_6045

Nešović M, Podolski-Renić A, Stanković T, Divac Rankov A, Fallacara AL, Schenone S, Botta M, Pešić M, Dinić J. The potential of c-Src inhibitors Si306 and pro-Si306 for suppressing invasion and overcoming multidrug resistance in glioblastoma. in COST Action CM1407: Challenging organic syntheses inspired by naturefrom natural products chemistry to drug discovery: Meeting dedicated to Early career Investigators; 2019 Feb 18-19; Brussels, Belgium. 2019;:9-9.
https://hdl.handle.net/21.15107/rcub_ibiss_6045 .

Nešović, Marija, Podolski-Renić, Ana, Stanković, Tijana, Divac Rankov, Aleksandra, Fallacara, Anna Lucia, Schenone, Silvia, Botta, Maurizio, Pešić, Milica, Dinić, Jelena, "The potential of c-Src inhibitors Si306 and pro-Si306 for suppressing invasion and overcoming multidrug resistance in glioblastoma" in COST Action CM1407: Challenging organic syntheses inspired by naturefrom natural products chemistry to drug discovery: Meeting dedicated to Early career Investigators; 2019 Feb 18-19; Brussels, Belgium (2019):9-9,
https://hdl.handle.net/21.15107/rcub_ibiss_6045 .

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 . .