UBP684 is a novel NMDAR PAM (positive allosteric modulator) which robustly potentiates responses at all GluN1/GluN2 subtypes and at neuronal NMDARs. UBP684 increases the maximal l-glutamate/glycine response while having minor subunit-specific effects on agonist potency.
UBP684 increases NMDAR channel open probability (Po) and slows receptor deactivation time upon removal of L-glutamate but not glycine.
Docking studies suggest that UBP684 binds to the GluN1 and GluN2 LBD (ligand binding domain) interface supporting its potential ability in stabilizing the LBD closed conformation.
UBP684 binding is independent of agonist binding and its activity is independent of membrane voltage and redox state. UBP684 activity is also pH-dependent, with enhanced potentiation at lower pHs and inhibitory activity at high pH (e.g.8.4).