Mibefradil inhibition of the Cole-Moore shift and K⁺-conductance of the tumor-related Kv10.1 channel

Correction to: Inhibition of the K+ conductance and Cole-Moore shift of the oncogenic Kv10.1 channel by amiodarone

“…It is worth to mention that we recently published [10,11] that mibefradil, a water-soluble compound up to a 30-mM concentration (in contrast to amiodarone which is water-insoluble), exerts similar effects on Kv10.1 channels than those reported here for Ad. In the case of mibefradil, we hypothesized that it modifies Kv10.1 gating by binding to the S1-S4 voltage sensor module [10,11]. It is intriguing why two different compounds having so markedly different water solubility exert effects so qualitatively similar on Kv10.1.…”

Overcoming challenges of HERG potassium channel liability through rational design: Eag1 inhibitors for cancer treatment

“…Accessibility of the VSD from the cell's outer side allows molecules to modulate the channel without crossing the membrane, like toxins do. [154][155][156][157] Most of the known small molecules that modulate Eag1 activity first cross the cell membrane and bind to the intracellular side of the channel. A majority of those compounds are pore blockers that physically occlude Gating-modifiers (1-5, Figure 5) mostly change the kinetics of the channel activation, inactivation, or deactivation by binding to the PD or VSD of the channel (Figure 4).…”

“…The VSD has binding sites for small molecules that act as gating modifiers (molecules 1, 2, 4, 6 , and 7 , Figure 4). Accessibility of the VSD from the cell's outer side allows molecules to modulate the channel without crossing the membrane, like toxins do 154–157 . Most of the known small molecules that modulate Eag1 activity first cross the cell membrane and bind to the intracellular side of the channel.…”