Biochem/physiol Actions

GNE-9278 is a selective NMDAR, but not AMPAR, positive allosteric modulator (PAM fold enhancement Emax/EC50 = 5.5/0.74 µM/2A, 8.4/3.07 µM/2B,10.2/0.47 µM/2C, 7.9/0.32 µM/2D of gly EC50 (50 µM)-induced Ca++ influx in HEK293 co-expressing GluN1 & respective GluN2 subunit; Emax/EC50 = 4.6/3.2 µM/2A,12.4/15.7 µM/2B, 9.1/6.6 µM/2C, 14.9/6.7 µM/2D of 100 µM Glu-induced current in the presence of 50 µM gly using respective GluN1/GluN2 oocytes). GNE-9278 targets transmembrane domain (TMD) extracellular surface of agonist-bound NMDARs, stabilizing NMDARs in an activated state by slowing L-L-glu & gly off-rate.