Exploration of the potential neuroprotective compounds targeting GluN1-GluN2B NMDA receptors

The N-methyl-d-aspartic acid (NMDA) receptors belongs to the family of ionotropic glutamate receptors, which could mediate most excitatory synaptic transmission in the brain. It is interesting to know if some available drugs have regulatory effects on the NMDARs. Herein, the present study reports the discovery of drugs targeting NMDAR using virtual screening. In this study, talniflumate with the EC50 value at 61.49 nM was successfully screened. The interaction analysis of this compound was further explored through molecular dynamics simulation. It is indicated that talniflumate could form stable interactions with GluN1-GluN2B NMDA receptors. In particular, H-bond interactions with high occupancies between GluN1-GluN2B NMDA receptors and talniflumate were observed. Compared to de novo drug discovery, this approach could be an alternative choice for development of safety and efficiency NMDAR inhibitors from available drugs.Communicated by Ramaswamy H. Sarma.