GPE (Glycine-Proline-Glutamate)

Research-Grade

GPE (Glycine-Proline-Glutamate, also called cyclo-glycyl-proline or IGF-1(1-3)) is the N-terminal tripeptide that is enzymatically cleaved from circulating IGF-1 in the brain. Despite its small size, GPE has demonstrated significant neuroprotective properties independent of the IGF-1 receptor — suggesting it acts through its own signaling pathway. In preclinical stroke models (MCAO in rats), GPE administration reduced infarct volume by 40–60% when given within a 4-hour therapeutic window. The mechanism appears to involve NMDA receptor modulation (reducing excitotoxicity), anti-inflammatory effects (reducing microglial activation), and anti-apoptotic signaling. GPE also promotes astrocyte uptake of glutamate, directly addressing the excitotoxic cascade that drives secondary brain injury. A modified analog, NNZ-2566 (trofinetide), advanced through human clinical trials and received FDA approval in 2023 for Rett syndrome under the brand name Daybue — validating the GPE pharmacophore as a clinically meaningful neuroprotective scaffold.