PE-22-28 is a synthetic 7-amino-acid peptide derived from the blood-degradation products of Spadin, an antidepressant peptide first identified from the propeptide of sortilin/NTSR3. It is the shortest and most potent published analog of Spadin and one of the few compounds in research-vendor catalogues with a clean published mechanism of action — selective inhibition of the TREK-1 potassium channel. This monograph lays out its chemical identity, TREK-1 pharmacology, the published research record, and how it relates to the parent Spadin molecule.
Chemical identity and structure.
PE-22-28 is a 7-residue peptide ("mini-spadin"), derived from spadin via systematic analog work characterised in Frontiers in Pharmacology and related publications. The compound is supplied as a lyophilized white-to-off-white powder, water-soluble. Its short sequence and small size are central to the published improvements over parent spadin: stronger TREK-1 affinity and substantially longer in-vivo half-life.
Mechanism of action.
PE-22-28 is a selective TREK-1 channel inhibitor. Published in-vitro work reports an IC50 of approximately 0.12 nM at TREK-1 — roughly 300-fold more potent than parent spadin (IC50 ~40 nM) — with confirmed selectivity over TREK-2, TRAAK, TRESK, and TASK-1. TREK-1 is a two-pore-domain potassium channel whose pharmacological blockade is the published mechanistic basis for the antidepressant effects characterised across the Spadin / PE-22-28 series.
Research applications and the evidence base.
Published research on PE-22-28 is concentrated in CNS pharmacology — antidepressant behavioural models in rodents (forced-swim test, tail-suspension test) where PE-22-28 and its derivatives have shown significant reductions in immobility time, with sustained action duration up to ~23 h (vs ~7 h for parent spadin). The compound has been used as a research tool to dissect TREK-1's role in mood regulation. There is no completed human clinical trial of PE-22-28 as of this writing.
Research context.
PE-22-28 sits in the small but well-defined family of TREK-1 modulators developed from the sortilin propeptide. Researchers studying TREK-1 pharmacology, sortilin biology, or non-monoaminergic antidepressant mechanisms work with PE-22-28 as the most potent published peptide tool. It is not a peptide for general nootropic or cognitive research — the published evidence base is narrowly TREK-1 / antidepressant-focused.
Storage and handling.
Lyophilized PE-22-28 should be kept refrigerated (2–8 °C) and protected from light. The peptide does not tolerate repeated freeze-thaw cycles or vigorous shaking.
Quality and COA considerations.
A meaningful COA should confirm identity via mass spectrometry against the expected molecular weight of the 7-residue sequence, purity by HPLC (≥98% benchmark), and N- and C-terminal modification status — published spadin analogs explore both free and modified termini, and product identity depends on which terminal configuration is in the vial. Sterility and endotoxin testing should be reported for any vial intended for injection-model use.
Research-use note: This monograph is an educational summary of the published research literature on PE-22-28. The compound has not been evaluated in completed human clinical trials and is not approved for human use in any jurisdiction known to VialTalk. Nothing here is medical advice or a usage recommendation.