Evidence Grade E — Very limited evidence. 1 published studies. 0 registered clinical trials.
Medically reviewed by a licensed medical professional
PE-22-28 is a synthetic peptide that targets a specific potassium channel (TREK-1) in the brain, derived from a natural regulatory peptide called spadin. All research comes from a single French laboratory. No human clinical trials have been conducted. It has no regulatory approval.
PE-22-28 is also known by these brand and alternate names:
1 published studies: 0 human, 0 animal, 1 in-vitro, 0 reviews
PE-22-28 has no marketing authorisation. No human clinical trials have been conducted. The preclinical evidence comes predominantly from a single research group at a French institution.
Animal studies have used the forced swim test — a behavioural assay whose predictive validity for human outcomes is debated in the scientific community. No human pharmacokinetic, safety, or efficacy data exist. Products available through unregulated channels lack pharmaceutical quality assurance.
Research in animal models suggests PE-22-28 blocks the TREK-1 potassium channel with high selectivity at very low concentrations. TREK-1 channels are expressed in brain regions associated with mood regulation. These observations come from mouse behavioural studies and electrophysiology experiments conducted by a single laboratory.
Research suggests rigorous laboratory electrophysiology and multiple animal behavioural studies support the mechanism, with the TREK-1 target validated by human genetic data. The compound shows high selectivity and potency at very low concentrations. However, no human data of any kind exist, limited independent replication has been published outside the originating group, and poor oral bioavailability limits practical use. The behavioural tests used in animals (such as the forced swim test) have debated predictive validity for human outcomes. Products from unregulated channels lack pharmaceutical quality assurance.
PeptideTrace tracks 0 registered clinical trials for PE-22-28 sourced from ClinicalTrials.gov.
No trials registered on ClinicalTrials.gov for this compound.
PE-22-28 is a 7-amino-acid truncated analogue of spadin, derived from the propeptide of the sortilin receptor. It represents the minimal pharmacophore for TREK-1 potassium channel inhibition. Its sequence is Gly-Val-Ser-Trp-Gly-Leu-Arg (GVSWGLR), with molecular formula C35H55N11O9 and molecular weight 773.89 g/mol (CAS: 1801959-12-5; PubChem CID: 165437303). Duration of action is up to 23 hours in animal models, compared to 7 hours for parent spadin. Solubility is approximately 2 mg/mL in water. Research administration routes include intraperitoneal and subcutaneous injection, as well as intranasal delivery. Not approved by any regulatory agency.
PE-22-28 is a potent and selective blocker of TREK-1 (K2P2.1) two-pore domain potassium channels with an IC50 of 0.12 nM, approximately 333-500x more potent than parent spadin (IC50 approximately 40-60 nM). At 100 nM, research suggests no significant effect on TREK-2, TRAAK, TRESK, TASK-1, or critically, no effect on hERG channels (cardiac safety). The rationale traces to a 2006 study by Heurteaux et al. in Nature Neuroscience: TREK-1 knockout mice displayed a depression-resistant phenotype across five behavioral models. TREK-1 blockade depolarizes neurons, increases 5-HT neuron firing rate in the dorsal raphe nucleus, and accelerates hippocampal neurogenesis. Research suggests PE-22-28 exhibits a biphasic dose-response: neuroprotective TREK-1 activation at low doses (0.03 ug/kg) and antidepressant-like TREK-1 inhibition at higher doses (3 ug/kg).
All data is preclinical, predominantly from the IPMC/CNRS group at Universite Cote d'Azur (Mazella, Borsotto, Heurteaux). Djillani et al. (2017, Front. Pharmacol.) showed that in C57Bl/6J mice, PE-22-28 (3-4 ug/kg IP) significantly reduced immobility in the forced swim test (p < 0.001) at approximately 30x lower doses than spadin. Effects lasted up to 23 hours. Four-day treatment induced hippocampal neurogenesis (BrdU incorporation) and increased PSD-95 expression (synaptogenesis). Pietri et al. (2019, Neuropharmacology) demonstrated that in a mouse MCAO stroke model, sequential low-then-high dosing prevented post-stroke depression, improved motor/cognitive deficits, and enhanced neurogenesis persisting 10 weeks post-trauma. Human genetics context: TREK-1 (KCNK2) SNPs were associated with antidepressant response in the STAR*D clinical study (Perlis et al., 2008). No human trials have been conducted. No brand names exist.
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
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This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
