Screening lead compounds for QT interval prolongation

Abstract

The late detection of cardiotoxic side effects, such as QT prolongation, induced by compounds of pharmacological interest can dramatically impede drug discovery and development projects, and consequently increase their cost. The launch of new drugs with undetected cardiotoxic side effects could have hazardous consequences and could trigger lethal cardiac dysrhythmias in patients. It is desirable, therefore, to test for the potential cardiotoxic side effects of compounds at an early stage of drug development. Electrophysiological test systems and cellular-based fluorometric high-throughput assays are now available for cloned human cardiac ion channels. These test systems are important tools in the preclinical safety evaluation of drugs and newly developed compounds.