Validation of an impedance-based phenotypic screening assay able to detect multiple mechanisms of chronic cardiotoxicity in human stem cell-derived cardiomyocytes
Presentation
Presentation title
Validation of an impedance-based phenotypic screening assay able to detect multiple mechanisms of chronic cardiotoxicity in human stem cell-derived cardiomyocytes
Author
Marc Rogers, CSO Metrion Biosciences
Overview
Presentation by Marc Rogers, CSO Metrion Biosciences, Nanion technologies Exhibitor session, 2020 Biophysical Society meeting, San Diego USA.
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Background
CiPA is designed to address drug-induced cardiac arrythmia (TdP) and the acute effects of drug discovery compounds (minutes – hours) with a focus on plasmalemmal ion channels that underlie the cardiac action potential.
However, new and existing drugs can also cause structural cardiotoxicity, produced by a diverse set of chemical compounds and primary target mechanisms. These chronic effects can appear after days, weeks or months; and not all are reversible.
Classic examples include:
- Chemotherapy agents used for clinical oncology
- Anthracyclines such as Doxorubicin (breast cancer)
- Tyrosine kinase inhibitors (TKI) such as the ‘nibs
- Proteosome inhibitors such as Bortezomib
- HDAC inhibitors such as the ‘stats (some of which may also cause QTc prolongation)
Safety pharmacology testing therefore needs a reliable & predictive assay for chronic cardiotoxicity.
Other recommended Presentations
- M-type K+ channels in nociceptive pathways: physiological roles and therapeutic potential
- In depth profiling of human iPSC cardiomyocytes: From electrophysiology to phenotypic assays
- Utility of human iPSC derived CMs for preclinical safety assays and disease modelling
- Therapeutic potential of activators of two-pore domain ion channels
- Modulation of voltage-gated calcium channels in disease
Marc Rogers gave this presentation at the Nanion technologies Exhibitor session, 2020 Biophysical Society meeting, San Diego USA. More insights from Mark can be found in our ConnectIONS blog here.
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