The discovery of subunit-selective GluN1/GluN2B NMDAR antagonist via pharmacophere-based virtual screening.

ABSTRACT: The incidence and mortality rates of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are gradually increasing worldwide. Numerous studies have demonstrated that N-methyl-D-aspartic acid receptor (NMDAR)-mediated excitotoxicity contributes to neurodegenerative diseases. Ifenprodil, a subtype-selective NMDAR antagonist, showed strong therapeutic potential. However, it suffers from low oral bioavailability and off-target side effects. In this study, natural compounds were identified for selective inhibition of GluN1/GluN2B NMDAR of human. We obtained a set of natural compounds (n = 81,366) from COCONUT, TIPdb, PAMDB, CMNPD, YMDB, and NPAtlas databases, and then virtually screened by an ifenprodil-structure-based pharmacophore model and molecular docking

SUBMITTER: Tang J 

PROVIDER: S-EPMC10854469 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature