BNC375

**BNC375** is a potent, selective, and orally available type I positive allosteric modulator (PAM) of the α7 nicotinic acetylcholine receptor (α7 nAChR), with an EC50 of 1.9 μM. It potentiates acetylcholine-evoked α7 currents without significantly affecting receptor desensitization kinetics, addressing limitations of orthosteric agonists such as off-target activity and inverted U-shaped dose-response curves. Developed by Bionomics and licensed to Merck & Co (MSD), it demonstrates robust procognitive effects in preclinical models including scopolamine-induced deficits in rat novel object recognition, rhesus monkey object retrieval detour task, and aged monkey performance, with good CNS penetration, oral bioavailability, and broad dose-range efficacy. It is a clinical candidate for cognitive impairment in CNS disorders like Alzheimer's disease and schizophrenia.[1][2][3][4][11]