The Lysosomal Sequestration of Tyrosine Kinase Inhibitors and Drug Resistance
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Cell Culture
2.3. Assay for Determination of Intracellular IM Levels
2.4. Assay for Determination of Intracellular NIL Levels
2.5. Assay for Determination of Intracellular DAS Levels
2.6. Calculation of TKIs in Lysosomes
2.7. Western Blot Analysis
2.8. Activity of Lysosomal Hydrolases
2.9. LysoTracker Red Staining
2.10. Statistical Analysis
3. Results
3.1. Lysosomal Sequestration of TKIs
3.2. Lysosomal Sequestration of TKIs and Extracellular Drug Level
3.3. Lysosomal Sequestration of TKIs and Their Accessibility to Intracellular Targets
3.4. Stimulation of Lysosomal Sequestration Capacity by Sunitinib
3.5. Sequestration of TKIs in Sunitinib-Stimulated Lysosomes and Extracellular Drug Levels
3.6. The Sequestration of TKIs in Sunitinib-Stimulated Lysosomes and Their Accessibility to Intracellular Targets
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Drug | pKa 1 | log P 2 | Molecular Structure 3 |
---|---|---|---|
Imatinib | 8.27 | 4.38 | |
Nilotinib | 5.92 | 5.36 | |
Dasatinib | 7.22 | 3.82 |
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Ruzickova, E.; Skoupa, N.; Dolezel, P.; Smith, D.A.; Mlejnek, P. The Lysosomal Sequestration of Tyrosine Kinase Inhibitors and Drug Resistance. Biomolecules 2019, 9, 675. https://doi.org/10.3390/biom9110675
Ruzickova E, Skoupa N, Dolezel P, Smith DA, Mlejnek P. The Lysosomal Sequestration of Tyrosine Kinase Inhibitors and Drug Resistance. Biomolecules. 2019; 9(11):675. https://doi.org/10.3390/biom9110675
Chicago/Turabian StyleRuzickova, Eliska, Nikola Skoupa, Petr Dolezel, Dennis A. Smith, and Petr Mlejnek. 2019. "The Lysosomal Sequestration of Tyrosine Kinase Inhibitors and Drug Resistance" Biomolecules 9, no. 11: 675. https://doi.org/10.3390/biom9110675