Description
PE-22-28, also known as Mini-Spadin, is a synthetic heptapeptide corresponding to residues 22-28 of spadin, a naturally occurring peptide cleaved from the propeptide of sortilin (encoded by the SORT1 gene) during Golgi processing. Spadin was identified in a 2010 PLoS Biology paper by Mazella and colleagues as an endogenous TREK-1 potassium channel inhibitor with antidepressant-like properties in rodent models. PE-22-28 is studied in nootropic peptide CNS research as a selective K2P channel research tool, occupying a mechanistic position entirely distinct from both receptor-mediated neurotrophic peptides such as Semax and established CNS research compounds targeting monoamine or glutamate systems. All published evidence is preclinical; no completed human clinical trials exist.
Chemical Information
- Chemical Name: PE-22-28 (Mini-Spadin; spadin fragment 22-28)
- Also Known As: Mini-Spadin; spadin 22-28
- Parent Compound: Spadin (17-residue sortilin propeptide fragment)
- Compound Class: Synthetic heptapeptide K2P channel inhibitor (TREK-1 selective)
- Length: 7 amino acids (residues 22-28 of spadin)
- Primary Target: TREK-1 (TWIK-related K+ channel 1; K2P two-pore-domain potassium channel)
- Binding Affinity: IC50 approximately 0.12 nM (vs 40-60 nM for parent spadin)
- In vivo stability: Up to 23 hours (vs approximately 7 hours for spadin)
- PubChem CID: 165437303
- Production: Solid-phase peptide synthesis (SPPS)
Applications
- TREK-1 potassium channel pharmacology research. PE-22-28 provides a defined, high-affinity tool compound (IC50 0.12 nM) for studying TREK-1 channel inhibition in neuronal cell models. Its selectivity for TREK-1 over other K2P family members makes it appropriate for experiments where channel-specific inhibition is required
- K2P two-pore-domain channel biology. TREK-1 belongs to the K2P family of background leak channels that set resting membrane potential in neurons. PE-22-28 is studied as a pharmacological tool for probing how K2P channel activity affects neuronal excitability, neurotransmitter release, and circuit-level signaling in hippocampal and cortical cell models
- Hippocampal neurogenesis research. Published rodent data documents adult hippocampal neurogenesis induction within days of PE-22-28 administration. Researchers studying the relationship between K2P channel inhibition and adult neurogenesis use this compound as the primary tool for this mechanistic question
- TREK-1 and serotonergic circuit research. TREK-1 is expressed in dorsal raphe serotonergic neurons where it regulates their excitability; a 2026 Neuropharmacology study (Song et al.) connected TREK-1 blockade to the antidepressant mechanism of hydroxynorketamine, positioning TREK-1 as a convergence point for multiple CNS signaling pathways; PE-22-28 provides a peptide-based tool for studying this channel in serotonergic circuit models
- Sortilin biology and spadin structure-activity research. PE-22-28 is a truncated analog of spadin, itself a cleavage product of the sortilin propeptide. Researchers studying sortilin processing, propeptide fragment pharmacology, and the structure-activity relationships of spadin analogs use PE-22-28 as the optimized reference compound in this series
- Mechanistic comparison with monoamine and glutamate system research tools. PE-22-28’s K2P channel mechanism is distinct from all current classes of CNS research tools targeting monoamine reuptake transporters, NMDA receptors, or serotonin receptors. It enables study of a genuinely independent neurobiological pathway in models designed to dissect antidepressant-relevant neurobiology
Storage and Handling
Store as lyophilized powder at -20C for long-term stability, or at 2-8C for short-term use. Protect from heat, moisture, and direct light. Reconstitute immediately before use and avoid repeated freeze-thaw cycles. The improved in vivo stability of PE-22-28 relative to spadin reflects structural optimization. Still, maintain lyophilized storage conditions for long-term compound integrity.
Compliance Notice
PE-22-28 is for laboratory research use only. It is not for human or veterinary use and carries no therapeutic, diagnostic, or clinical indication. FDA has not evaluated this product. By purchasing this product, the buyer confirms that they will follow appropriate institutional safety procedures and use it exclusively for controlled research.
