Discovery of novel positive allosteric modulators targeting GluN1/2A NMDARs as anti-stroke therapeutic agents.

ABSTRACT: Excitotoxicity due to excessive activation of NMDARs is one of the main mechanisms of neuronal death during ischemic stroke. Previous studies have suggested that activation of either synaptic or extrasynaptic GluN2B-containing NMDARs results in neuronal damage, whereas activation of GluN2A-containing NMDARs promotes neuronal survival against ischemic insults. This study applied a systematic in silico, in vitro, and in vivo approach to the discovery of novel and potential GluN1/2A NMDAR positive allosteric modulators (PAMs). Ten compounds were obtained and identified as potential GluN1/2A PAMs by structure-based virtual screening and calcium imaging. The neuroprotective activity of the candidate compounds was demonstrated in vitro. Subsequently, compound 15 (a

SUBMITTER: Zhu H 

PROVIDER: S-EPMC11042165 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature