Cor.At® mouse stem cell-derived cardiomyocytes provide a predictive, standardized, and reproducible cell system for the in vitro assessment of structural carditoxicity (e.g. viability, metabolic impairment). After incubation with test compounds, end points such as neutral red uptake can be used to determine effects which directly affect the viability and integrity of cardiac cells when compared to a non-specific reference cell type, e.g. mouse fibroblasts. Cor.At® cardiomyocytes can also be used to detect effects of compounds on mitochondrial function and levels of cardiac-specific troponin release.
The Cor.At@ Tox assay improves the ability to determine potential cardiotoxic effects of compounds in early stages of drug development, thus providing better measures to move lead compounds towards preclinical and clinical development.
The Cor.At® Tox Assay has been validated in-house using 40 drugs with known cardiac safety profile to predict cardiac specific cytotoxicity of test compounds. The validation study revealed specificity, sensitivity, and positive and negative predictive values of > 90% each. Reference compounds run within each test ensure reproducible results.
Figure 1: Effect of 3 Anthracyclins in the NRU Assay on Cor.At Cardiomyocytes and Mouse Fibroblasts.
Advantages of the Cor.At Tox / Neutral Red Uptake Assay
- Predictive, relevant and robust test system capable of medium to high throughput screening.
- Early and quick results on structural cardiotoxicity, time- and cost effective.
- Either standardized or customized protocols available with respect to drug treatment period, concentrations, and read-out.
- Comparison with effects on cardiac electrophysiology and mitochondrial function within the same cell system possible.
- Library-specific validation studies possible.