“…However, the exact molecular determinants of hERG activator function remain unresolved, with most of the knowledge about possible binding sites derived from mutagenesis experiments. Sangunetii et al found that two groups of residues have different effects on RPR260243 [24,37] . One group, including L553, F557 (S5), and N658, V659 (S6), affects the inactivation and deactivation effect of RPR260243 on the hERG channel, while mutations in the other group of residues, including V549, L550 (S4-S5 linker), and I662, L666, Y667 (intracellular S6 segment), only hinder the transition to the closed state of the channel.…”