Aging Model for Analyzing Drug-Induced Proarrhythmia Risks Using Cardiomyocytes Differentiated from Progeria-Patient-Derived Induced Pluripotent Stem Cells
Abstract
:1. Introduction
2. Results
3. Discussion
4. Methods
4.1. iPSC Culture
4.2. iPSC Differentiation and Cardiomyocyte Purification
4.3. Compounds
Drug | Category | Cmax [nM] | Dose1 [nM] | Dose2 [nM] | Dose3 [nM] | Dose4 [nM] |
---|---|---|---|---|---|---|
Dofetilide | High | 2.14 | 0.3 | 1 | 3 | 10 |
Bepridil | High | 31.5 | 35 | 105 | 210 | 315 |
Quinidine | High | 843 | 100 | 300 | 900 | 2700 |
Terfenadine | Mid | 0.286 | 0.08 | 0.8 | 8 | 80 |
Chloroquine | Mid | 250 | 250 | 750 | 2500 | 25,000 |
Chlorpromazine | Mid | 34.5 | 35 | 350 | 1050 | 3500 |
Cisapride | Mid | 2.58 | 2.5 | 7.5 | 25 | 125 |
Diltiazem | Low | 128 | 3 | 10 | 30 | 90 |
Mexiletine | Low | 2500 | 625 | 1250 | 2500 | 3750 |
Ranolazine | Low | 1948 | 1000 | 2300 | 6900 | 15,000 |
Verapamil | Low | 45 | 1 | 10 | 50 | 150 |
4.4. Assay
4.5. Radial Plots
4.6. Logistic Regression
- model = LogisticRegression(multi_class = ‘multinomial’, solver = ‘lbfgs’, random_state = 0, max_iter = 1000)
- result = model.fit(x_train,y_train)
- probabilities = model.predict_proba(drug)
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Daily, N.; Elson, J.; Wakatsuki, T. Aging Model for Analyzing Drug-Induced Proarrhythmia Risks Using Cardiomyocytes Differentiated from Progeria-Patient-Derived Induced Pluripotent Stem Cells. Int. J. Mol. Sci. 2023, 24, 11959. https://doi.org/10.3390/ijms241511959
Daily N, Elson J, Wakatsuki T. Aging Model for Analyzing Drug-Induced Proarrhythmia Risks Using Cardiomyocytes Differentiated from Progeria-Patient-Derived Induced Pluripotent Stem Cells. International Journal of Molecular Sciences. 2023; 24(15):11959. https://doi.org/10.3390/ijms241511959
Chicago/Turabian StyleDaily, Neil, Julian Elson, and Tetsuro Wakatsuki. 2023. "Aging Model for Analyzing Drug-Induced Proarrhythmia Risks Using Cardiomyocytes Differentiated from Progeria-Patient-Derived Induced Pluripotent Stem Cells" International Journal of Molecular Sciences 24, no. 15: 11959. https://doi.org/10.3390/ijms241511959