Figure 5.

Predictive performance of the QMOD pocketmol was assessed on the molecules for which log odds was non-negative, resulting in 27 molecules with measured hERG activity. Rank correlation was highly statistically significant (see text for details). The points in the plot labeled with letters correspond to the molecules from Figure 2, all withdrawn from the market due to cardiac issues involving long-QT: astemizole (A), cisapride (B), terfenadine (C), mibefradil (D), and thioridazine (E), the first three of which are shown in poses from fit into the pocketmol (test molecules in cyan, E-4031 in green, and the volume swept by the majority of training molecules in transparent orange). The points in the blue circles correspond to sildenafil and trazodone, both of which have clinical reports of cardiac side effects and dose-dependent hERG blockade. The points in the green circles correspond to amiodarone, dronedarone, and propafenone, all of which are cardiac anti-arrhythmics and which modulate hERG.