Drug-induced cardiotoxicity is one of the major reasons a compound can experience late-stage attrition during development due to its common association with potentially fatal Torsades de Pointes arrhythmias. These adverse effects can be detected by prolongation of the QT interval, which is mostly human Ether-à-go-go-Related Gene (hERG) channel connected. In this presentation, we investigate the possibility of using known hERG blockers, E-4031 and Sotalol, to induce irregular beating patterns in the mouse and human induced pluripotent stem cell derived (miPSC and hiPSC) cardiomyocyte model systems, which can be rescued back to normal beating patterns by subsequent opening of the hERG channel using the enhancer compound Nicorandil. All experiments were carried out using an AFM-based approach to precisely monitor the beating interval of cardiomyocytes, and therefore verification was implemented using three individual cardiovascular compounds with comparison to previously reported methods. This represents that AFM can serve as a sensible pre-screening tool for use during drug development.

Evaluation of drug-mediated changes in cardiomyocytes by AFM

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.