Dual Anta-Inhibitors Targeting Protein Kinase CK1δ and A2A Adenosine Receptor Useful in Neurodegenerative Disorders
Abstract
1. Introduction
2. Results and Discussion
3. Materials and Methods
3.1. Test Materials
3.2. Animals
3.3. Cells Culture
3.4. Cell Titer 96® Aqueous One Solution Cell Proliferation Assay
3.5. CellTiter-Glo® Luminescent Cell Viability Assay
3.6. Griess Assay
3.7. Everted Gut Sac Studies
3.8. HPLC-MS Analysis
3.9. Calculation of the Apparent Permeability Coefficients
3.10. Percentage of Drug Absorption (A%) and Drug Retention (Ad%)
3.11. Statistical Analysis
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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A | B | |||||
---|---|---|---|---|---|---|
Cmp | KiA1 (μM) a | KiA2A (μM) b | KiA3 (μM) c | % Residual Activity at 40 μM ± sd | % Residual Activity at 10 μM ± sd | IC50 (μM) |
1 | 3.339 ± 0.658 | 0.123 ± 0.002 | 2.878 ± 0.695 | 19 ± 9.4 | 27 ± 4.0 | 1.75 ± 0.2 |
2 | 2.903 ± 0.648 | 0.0762 ± 0.173 | 1.146 ± 0.107 | 22 ± 1.0 | 34 ± 5.0 | 0.59 ± 0.2 |
3 | 0.118 ± 0.010 | 0.007 ± 0.00001 | 0.140 ± 0.035 | 86 ± 1.6 | n.d. | >40 |
4 | 8.657 ± 1.524 | 3.478 ± 0.312 | 5.957 ± 1.021 | 25 ± 9.6 | 13 ± 24 | 0.36 ± 0.1 |
ZM 241385 | 348 ± 11 | 1.250 ± 0.21 | 1072 ± 207 | - | - | - |
PF-670462 | - | - | - | - | - | 0.014 [33] |
Initial Concentration | Absorbed Concentration |
---|---|
24.6 | 11.5 |
2.46 | 1.03 |
0.246 | 0.059 |
Initial Concentration | Absorbed Concentration |
---|---|
37.6 | 8.66 |
3.76 | 0.576 |
0.376 | - |
Concentration | Percentage of Drug Absorption (A%) | Percentage of Drug Retention (Ad%) | Papp (×10−6 cm/s) |
---|---|---|---|
10−4 M | 47 | 2 | 33 |
10−5 M | 42 | 10 | 29.6 |
10−6 M | 24 | 35 | 16.9 |
Concentration | Percentage of Drug Absorption (A%) | Percentage of Drug Retention (Ad%) | Papp (×10−6 cm/s) |
---|---|---|---|
10−4 M | 23 | 55 | 16.1 |
10−5 M | 15 | 66 | 10.8 |
10−6 M | - | - | - |
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Francucci, B.; Angeloni, S.; Dal Ben, D.; Lambertucci, C.; Ricciutelli, M.; Spinaci, A.; Smirnov, A.; Volpini, R.; Buccioni, M.; Marucci, G. Dual Anta-Inhibitors Targeting Protein Kinase CK1δ and A2A Adenosine Receptor Useful in Neurodegenerative Disorders. Molecules 2023, 28, 4762. https://doi.org/10.3390/molecules28124762
Francucci B, Angeloni S, Dal Ben D, Lambertucci C, Ricciutelli M, Spinaci A, Smirnov A, Volpini R, Buccioni M, Marucci G. Dual Anta-Inhibitors Targeting Protein Kinase CK1δ and A2A Adenosine Receptor Useful in Neurodegenerative Disorders. Molecules. 2023; 28(12):4762. https://doi.org/10.3390/molecules28124762
Chicago/Turabian StyleFrancucci, Beatrice, Simone Angeloni, Diego Dal Ben, Catia Lambertucci, Massimo Ricciutelli, Andrea Spinaci, Aleksei Smirnov, Rosaria Volpini, Michela Buccioni, and Gabriella Marucci. 2023. "Dual Anta-Inhibitors Targeting Protein Kinase CK1δ and A2A Adenosine Receptor Useful in Neurodegenerative Disorders" Molecules 28, no. 12: 4762. https://doi.org/10.3390/molecules28124762
APA StyleFrancucci, B., Angeloni, S., Dal Ben, D., Lambertucci, C., Ricciutelli, M., Spinaci, A., Smirnov, A., Volpini, R., Buccioni, M., & Marucci, G. (2023). Dual Anta-Inhibitors Targeting Protein Kinase CK1δ and A2A Adenosine Receptor Useful in Neurodegenerative Disorders. Molecules, 28(12), 4762. https://doi.org/10.3390/molecules28124762