Glypromate

Summary

Glypromate (Gly-Pro-Glu, GPE) is an endogenous tripeptide cleavage product of insulin-like growth factor-1 (IGF-1) that occurs naturally in the brain. It has demonstrated neuroprotective effects in preclinical models of hypoxic-ischemic brain injury, stroke, and neurodegeneration. Clinical development focused on perinatal asphyxia and stroke, but trials did not progress to approval. The synthetic analog NNZ-2566 (Trofinetide) was later developed from this scaffold.

Mechanism of Action

Glypromate (GPE) is an N-terminal tripeptide of IGF-1 that acts independently of IGF-1 receptors. It modulates glutamate release, reduces excitotoxicity, inhibits neuronal apoptosis, and has anti-inflammatory properties in the CNS. It may also interact with NMDA receptors to provide neuroprotection.

Routes of Administration

Goals & Uses

• Neuroprotection after hypoxic-ischemic brain injuryNeurologyModerate
• Stroke recovery and neuroprotectionNeurologyLow
• Traumatic brain injury treatmentNeurologyLow
• Reduction of neuroinflammationNeurologyLow

Contraindications

• Known hypersensitivity to GPE or its componentsAllergyHigh

Adverse Effects

• Injection site reactionsLocalUnknown
• HypotensionCardiovascularUnknownLow blood pressure
• Fever/pyrexiaSystemicUnknown

Drug Interactions

• NMDA receptor antagonistsLow

Population Constraints

• Renal impairmentOrgan ImpairmentRelative
• Pregnant womenReproductiveRelative
• NeonatesPediatricRelative

Regulatory Status

• European UnionInvestigationalNo marketing authorization; research and early clinical stage only
• United StatesInvestigationalInvestigated in early-phase trials; no IND progression to approval. Related analog trofinetide approved for Rett syndrome.
• United KingdomUnknownNo known UK-specific regulatory filing or approval

Not approved by any regulatory agency. Investigated in early-phase clinical trials for hypoxic-ischemic brain injury. The related analog NNZ-2566 (trofinetide) received FDA approval for Rett syndrome in 2023, but GPE itself remains unapproved.

Evidence & Sources

No sources recorded yet.