ST-2262

**ST-2262** is a selective small molecule inhibitor of the voltage-gated sodium channel **NaV1.7** (IC50 of 72 nM), blocking the extracellular vestibule with >200-fold selectivity over NaV1.1-1.6 and NaV1.8. Unlike many NaV1.7 inhibitors that prefer the inactivated state, it is equipotent across resting, inactivated, and high-frequency states. Developed as a potential non-opioid analgesic, it reduced sensitivity to noxious heat in non-human primates, establishing the extracellular vestibule as a viable site for selective NaV1.7 ligands. It also inhibits sympathetic and parasympathetic nerve-mediated responses in vascular and airway tissues.