Marc Rogers, CSO Metrion Biosciences

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.