GAT2711

GAT2711 is a potent, selective full agonist of α9 nicotinic acetylcholine receptors (nAChRs), exhibiting an EC50 of 230 nM and 340-fold selectivity over α7 nAChRs. Reversible binding at the α9(+)α9(-) interface is supported by molecular docking and electrophysiology studies, which show concentration-dependent inward currents in α9 nAChR-expressing Xenopus oocytes. GAT2771 demonstrates anti-inflammatory potential by inhibiting ATP-induced IL-1β release in THP-1 cells (IC50 = 0.5 μM) and human PBMCs (effective at 100 fM). In a complete Freund́s adjuvant (CFA)-induced inflammatory pain model, intraperitoneal administration (2 and 10 mg/kg) in mice, including α7 nAChR knockouts, produced potent, long-lasting (up to 72 hours) analgesic effects, suggesting an α9 nAChR-mediated mechanism for managing inflammatory and neuropathic pain.