BNC375 (BNC-375) is a potent, selective, orally available type I α7 nAChR positive allosteric modulator (PAM) with EC50 of 1.3 uM.
BNC375 significantly potentiated the acetylcholine signal without changing the rapid receptor desensitization.
BNC375 exhibited the MED of 0.03 mg/kg, and full reversal of the scopolamine-induced impairment was achieved at 1.0 mg/kg in mouse T-maze model.
BNC375 possessed an excellent safety profile: no change in the spatial and temporal response of the receptor to endogenous ligand ACh, no activity on other related channels, and no inhibition of major drug metabolizing enzymes such as CYP3A4, CYP2C9, CYP2D6, CYP1A2, and CYP2C19 (IC50 >10 uM).
