Understanding cardiac safety early is critical in drug development. In their latest poster, Jazz Pharmaceuticals, explain how they utilised Metrion’s clinically translatable cardiotoxicity assay to do exactly that.
The development of Automated Patch Clamp (APC) technology over the last 20 years has
transformed the research and development process for identifying novel drugs for ion channel targets. Furthermore, it has been widely implemented in cardiac safety pharmacology screening by pharma and contract research organisations.
The adoption of APC as a screening tool has gathered pace over the last 10 years, which may
in part be attributed to the introduction of the Comprehensive in Vitro Proarrhythmia Assay
initiative (CiPA and JiCSA in Japan). Several published studies have confirmed that the high
quality potency data derived from APC screening can be inserted into in silico models of human ventricular action potentials to accurately predict proarrhythmic risk.
Most commercially available APC cardiac safety assays have historically been performed at room temperature. However, it is widely acknowledged that temperature can affect the hERG potency of certain agents (e.g. erythromycin, sotalol), which underlies the basis of why the FDA recommend performing GLP hERG studies at physiological temperatures. Therefore, an APC assay performed at physiological temperatures will benefit from the combination of greater throughput with enhanced sensitivity for compounds that exhibit temperature dependent inhibition.
Understanding cardiac safety early is critical in drug development. In their latest poster, Jazz Pharmaceuticals, explain how they utilised Metrion’s clinically translatable cardiotoxicity assay to do exactly that.
Development of a robust hNaV1.9 high-throughput screening assay on the Sophion Qube384 platform. This is complemented by a suite of ion channel selectivity assays and sensory neuron recordings to create a versatile screening cascade to support NaV1.9 drug discovery programmes.