With a hit rate of ~30% observed across the industry (
Brennan et al. 2024) hERG channels have a high off-target hit rate that has a well-documented link to life-threatening cardiac arrythmias including Torsade de Pointes. Therefore, screening of novel compounds is essential to eliminate this liability early, before lead development, where it becomes more challenging to address.
Figure 1.
A. Graph showing the peak hERG tail current (recorded at 37 °C) plotted against time for a representative cell treated with 1 and 10 μM ondansetron followed by 1 μM E-4031. The inset figure shows representative current traces in 0.1% DMSO, ondansetron and E-4031.
B. Graph showing the mean ± SD inhibition data (purple symbols), as well as individual inhibition values (grey symbols), plotted against concentration. The data were fitted with a Hill equation to yield the half-maximal inhibition concentration (IC50) and the 95% confidence bands (red dashed lines).