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A Strategy to Investigate Potential Pro-Arrhythmic Effects of Compounds During the Drug Discovery and Development Process

Within the past years, the cardiac HERG ion channel was identified as a notorious target inducing cardiovascular side effects even of some marketed drugs. Several compounds have therefore been taken out of clinical studies or removed from the market. These compounds had diverse chemical structures and stem from different therapeutic areas. Interactions with other cardiac ion channels can however mitigate or exacerbate HERG effects.

For pharmaceutical companies it is not only essential to identify HERG interacting compounds early during the drug discovery and development process, but also to understand potential effects of compounds on the cardiac action potential. This helps to increase the safety for patients, and to avoid the costs of unsuccessful projects in later phases.