PE-22-28 is a synthetic heptapeptide analogue of Spadin with an approximate molecular weight of 773.89 g/mol. It is derived from the propeptide of the sortilin receptor and corresponds to a truncated fragment of the 44-amino acid Spadin peptide, retaining the minimal sequence associated with modulation of the TWIK-related potassium channel-1 (TREK-1). TREK-1 is a two-pore domain potassium channel (K2P2.1) expressed throughout the central nervous system and implicated in the regulation of neuronal excitability. Produced via solid-phase peptide synthesis, PE-22-28 is associated with TREK-1 channel modulation and monoaminergic signalling pathways.

PE-22-28 has been investigated in preclinical neuropharmacology as a minimal-length TREK-1 channel modulator and was developed as a shorter, more metabolically tractable analogue retaining the active pharmacophore. In vitro electrophysiology studies have documented that PE-22-28 inhibits TREK-1 currents recorded by whole-cell patch clamp in a TREK-1-expressing HEK cell line, blocking the arachidonic-acid-activated channel with markedly greater potency than the parent peptide, and have characterised it as the shortest Spadin-derived fragment retaining TREK-1 inhibitory activity [1]. In vivo rodent studies have examined the compound in behavioural pharmacology paradigms, documenting that PE-22-28 produced antidepressant-like effects in the forced swim, novelty-suppressed feeding and learned-helplessness paradigms and in a corticosterone-induced depression model, and that a four-day administration schedule increased hippocampal neurogenesis and cortical synaptogenesis markers, characterising the compound as active on behavioural and neuroplasticity readouts following systemic administration [1,2], making PE-22-28 a reference compound in preclinical neuropharmacology research examining Spadin-derived TREK-1 channel modulation and hippocampal neuroplasticity in rodent models.

PE-22-28 is manufactured in a cGMP compliant, ISO9001 certified laboratory to a guaranteed purity of 98% or above. Every batch is independently tested using HPLC and MS-UPLC analysis before dispatch. Vials are vacuum sealed and stored in a temperature controlled, monitored cold storage system. Certificates of Analysis are available on request.

Sold strictly for in vitro research purposes only. Not for human consumption. Intended for use by qualified researchers in laboratory settings only.

Editorial Team

Dr. Martina Rossi, PhD

Scientific Contributor and Reviewer

Reviewed and approved 14 June 2026

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