Predicting Tyrosine Kinase Inhibitor Cardiotoxicity with a Biomarker-Based Human iPSC-Derived Cardiomyocyte Assay [SOT 2019]
Presented at the Society of Toxicology Annual Meeting and ToxExpo in Baltimore, Maryland; March 2019.
Tyrosine kinase inhibitors (TKI) have greatly improved the treatment and prognosis for a wide range of cancers but often cause cardiotoxic effects. We developed an in vitro assay, Cardio quickPredict, for predicting cardiovascular liability based on changes in human iPSC-derived cardiomyocytes (iPSC-CM) metabolism and cell viability, which identifies both functional and structural cardiotoxicants.
The current study evaluated the utility of this assay for evaluating the cardiotoxicity potential of 10 TKIs that cause a range of functional and structural cardiotoxic effects. The Cardio quickPredict assay accurately identified the cardiotoxicity potential of the tested TKIs. The metabolic readout of this assay can be used in conjunction with other cardiotoxicity screens to provide a more comprehensive evaluation of a compound’s cardiovascular liability.
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