Repurposing of cefpodoxime proxetil as potent neuroprotective agent through computational prediction and in vitro validation.

In recent reports, NR2B-NMDA receptor antagonists showed more research value because of its strong targeting ability and less side effects potential. In 2016, EVT-101 was reported to bind in an almost entirely new binding region of this target. Whether strikingly different binding modes can improve targeting and reduce side effects is worth studying. In our preliminary work, we explored the binding patterns of ifenprodil and EVT-101, found the key amino acids and summarized the pharmacophores, hoping to find such antagonists that target the two binding modes simultaneously. In this study, we developed a scalable virtual screening workflow in the FDA-approved drugs library to identify novel NR2B-NMDAR antagonists based on the combination of two pharmacophores. Cefpodoxime proxetil (