hERG

hERG potassium channels play an essential role in normal electrical activity of the heart, mediating the cardiac action potential of the heartbeat. Affecting their activity by xenobiotics can have life-threatening consequences. Accordingly, hERG is one of the most important off-targets of drug discovery. Optimisation to reduce the risk of inhibiting the hERG channels during discovery projects requires computational prediction in the early design throughout the pre-synthesis phase. The hERG channel inhibition capacity of a drug is measured by its hERG activity (Act). Experimentally, hERG activity is determined by different electrophysiological methods and measured as IC50 or Ki values. However, as with other physico-chemical properties (e.g. pKa), the negative logarithm of the measured activity (pActivity) is used in the literature: pActivity = -log10(Act) Besides quantitative hERG values it is also common to provide a two-class classification of compounds for hERG activity.