The synthetic cannabinoid 5F-AKB48 effectively inhibits the hERG potassium channel by interacting with a noncanonical site involving M651 and F557 residues.
The synthetic cannabinoid 5F-AKB48 inhibits the hERG potassium channel via a noncanonical binding site, providing mechanistic insight into its potential proarrhythmic effects.
inhibition by the drug. In contrast, the F557L and M651A mutations significantly attenuated the inhibitory action of 5F-AKB48. In silicoAI-based modelling, docking, and molecular dynamics simulations provided further evidence for distinct binding modes involving M651 and F557. We conclude that 5F-AKB48 is an effective inhibitor of the hERG potassium channel that interacts with a site which is distinct from the canonical pore site involving S6 aromatic residues.
Cheng et al. (Thu,) conducted a other in hERG K+ channel inhibition. 5F-AKB48 was evaluated on hERG potassium channel inhibition. The synthetic cannabinoid 5F-AKB48 effectively inhibits the hERG potassium channel by interacting with a noncanonical site involving M651 and F557 residues.