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 dF508 mutation represents the most common cause underlying cystic fibrosis. The resultant misfolding of the nascent cystic fibrosis transmembrane regulator (CFTR) protein and its subsequent proteasomal degradation lead to a deficiency in functional CFTR channels and Cl- efflux at the apical cell membrane in ducts throughout the body (Veit et al. 2016). Small molecule drugs have been identified that rectify this protein misfolding (‘correctors’) and facilitate channel opening (‘potentiators’), thereby restoring CFTR-mediated Cl- efflux at the apical cell membrane and providing clinical improvement (Hanrahan et al. 2017).
Nevertheless, enhanced efficacy remains a key research goal, and evidence indicates that this could be achieved by combining correctors/potentiators with modulators of the ubiquitin proteasomal system (UPS) that regulates CFTR protein degradation (Borgo et al. 2022). There is growing interest in the development of novel treatments that utilise this dual-target approach; we therefore set out to demonstrate that we could:
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.