PE-22-28 is a 7-amino-acid peptide derived from a truncation of spadin, a natural peptide fragment of the sortilin propeptide. It acts as an antagonist of the TREK-1 potassium channel (TWIK-related K+ channel 1), which has been implicated as an antidepressant target. PE-22-28 has shown antidepressant-like effects in mouse behavioral models but remains an early-stage research tool compound with no human data whatsoever.
Category: Nootropic / Neuroprotective. Evidence rating: D (animal/preclinical only).
Clinical status: Preclinical tool compound only. No clinical trials. No regulatory evaluation.
PE-22-28 blocks the TREK-1 two-pore-domain potassium channel (KCNK2/K2P2.1), which is widely expressed in the brain. TREK-1 knockout mice display a depression-resistant phenotype, suggesting that TREK-1 blockade may have antidepressant effects. PE-22-28 is a more potent and shorter analog of…
Safety considerations: No human safety data exist; Mouse studies at antidepressant-effective doses did not report overt toxicity; TREK-1 channels are expressed in heart, vasculature, and GI tract — potential for off-target effects.
Reviewed by the PeptideAtlas Editorial Team. Last reviewed: 2026-07-05.
Related peptides: Semax, Cerebrolysin, Pinealon.
Compare: PE-22-28 vs Semax, PE-22-28 vs Cerebrolysin, PE-22-28 vs Pinealon.
Spadin is a 17-amino-acid peptide naturally produced by cleavage of the sortilin propeptide. It was identified as a natural TREK-1 channel blocker with antidepressant-like properties in mice. PE-22-28 is a shorter, more potent synthetic derivative of spadin.
It is too early to say. PE-22-28 is a preclinical tool compound that has shown promise in mouse behavioral models, but no human pharmacokinetic, safety, or efficacy studies have been conducted. The path from mouse behavioral testing to an approved antidepressant drug is long and uncertain.
Unknown. No human data of any kind exist for PE-22-28. Self-experimentation with a preclinical research compound carries unpredictable risks, particularly given TREK-1 expression in cardiac tissue.