Direct block of IKr by non-antiarrhythmic drugs is a major cause of QT prolongation and torsades de pointes (TdP), and has made the hERG potassium channel a major target of drug safety programs in cardiotoxicity. Adverse impact on the IKr repolarizing current and other cardiac ion channel currents has been shown to also be caused by trafficking inhibition of the channel from its site of synthesis and assembly in the endoplasmic reticulum (ER) to the cell surface. It has also been shown that channel blockers can act as pharmacological chaperones to rescue channel expression by allowing export from the ER and movement to the cell surface, partially or completely masking the underlying risk.
ChanTest has developed highly predictive, rapid assays for the detection of cardiac ion channel trafficking inhibition for safety and drug discovery. These assays, in conjunction with other cardiac safety assessments, help to provide a more complete picture of a compounds safety risk.