GS967

GS967 (also known as GS-458967) is a potent, small molecule inhibitor of the persistent (late) sodium current (Late INa). Developed by Gilead Sciences, it was originally designed as an antiarrhythmic agent targeting the cardiac sodium channel NaV1.5. Subsequent research has highlighted its potential in treating severe epilepsies, such as Dravet syndrome, where it demonstrates an unconventional mechanism compared to traditional sodium channel blockers. GS967 acts by stabilizing the inactivated state of voltage-gated sodium channels and has been shown to reduce the protein expression of NaV1.6 in the hippocampus. This dual action helps normalize the excitability of excitatory pyramidal neurons without negatively impacting inhibitory interneurons, thereby suppressing spontaneous seizures and improving survival in preclinical models.