PE-22-28 (Mini-Spadin): Research Overview

What is PE-22-28?

Synthetic heptapeptide derived from Spadin positions 22-28, functioning as potent TREK-1 antagonist with enhanced selectivity and duration versus parent compound. Primary research focus on rapid antidepressant effects.

What is PE-22-28 researched for?

• Primary research focus with rapid effects in behavioral models within 4 days.
• Anxiolytic properties demonstrated in preclinical anxiety models.
• Nearly doubles BrdU-positive cells after 4-day treatment.
• Promotes new synapse formation through CREB activation.
• Hippocampal and prefrontal cortex TREK-1 expression supports memory.
• Potential ischemic protection and neuronal survival support.
• PE-22-28 shows rapid antidepressant effects in animal models (within 4 days), but it's currently research-only with no human clinical trials completed. It's not approved for therapeutic use. However, the preclinical evidence is strong enough that clinical development may follow if pharmaceutical companies invest in it.

How does PE-22-28 work?

Selectively blocks TREK-1 potassium channels (IC50: 0.12 nM). Enhances serotonin neurotransmission in dorsal raphe nucleus, triggering CREB activation and hippocampal neurogenesis.

Reported targets: TREK-1

References

1. Shortened Spadin Analogs Display Better TREK-1 Inhibition

   2017

   PE-22-28 IC50 0.12 nM vs 40-60 nM for Spadin; ~23 hour duration. Frontiers in Pharmacology.

2. Spadin: A Sortilin-Derived Peptide Targeting TREK-1 Channels

   2010

   Original discovery of TREK-1 blockade as antidepressant mechanism. PLOS Biology.

3. TREK-1 Deletion Results in Depression-Resistant Phenotype

   2006

   TREK-1 knockout mice show depression-resistant behavior in 5 tests. Nature Neuroscience.

   Animal study