PE-22-28
PE-22-28 (often called mini-spadin) is a synthetic seven-amino-acid peptide derived from the sortilin propeptide that selectively blocks the TREK-1 potassium channel. In rodent models it is studied for rapid antidepressant-like effects and enhanced hippocampal neurogenesis. It has never been tested in humans and remains a research compound only.
Researchers investigating TREK-1 modulation, mood-related neuroscience, or hippocampal neurogenesis in preclinical models.
PE-22-28 was developed in 2017 by Djillani and colleagues as a shortened, optimized analog of spadin, a natural peptide cleaved from the sortilin propeptide and first described by Mazella's group in 2010. Structurally it corresponds to residues 22-28 of spadin, a seven-residue sequence engineered for greater potency and metabolic stability. Its target is TREK-1 (TWIK-related potassium channel 1), a two-pore-domain background potassium channel that normally lets potassium leak out of neurons and keeps them hyperpolarized.
By selectively inhibiting this leak current, PE-22-28 makes serotonergic neurons in regions such as the dorsal raphe nucleus more excitable, increasing 5-HT firing and downstream CREB phosphorylation and hippocampal neurogenesis. Reported preclinical potency is high, with an IC50 in the sub-nanomolar range and a substantially longer in vivo duration of action than spadin. In rodent behavioral assays such as the forced swim test it reduced immobility, a validated marker of antidepressant-like activity.
Importantly, all of this evidence comes from animal models; PE-22-28 is not FDA-approved, has no completed human efficacy or safety trials, and is sold strictly for research use only, so any use should occur under qualified physician guidance.
In rodent work PE-22-28 was given at ~3-4 mcg/kg/day; body-surface-area scaling puts the human-equivalent nearer ~0.5 mcg/kg (~35 mcg for a 70 kg adult). No human dose is established, so research protocols start very low — around 25-50 mcg subcutaneously once daily, ceiling ~100 mcg — and only under physician guidance.
Rodent studies suggest a rapid antidepressant-like signal within a few days of daily dosing, unlike the multi-week lag of conventional SSRIs; human onset is unknown.
Typically run standalone; no validated human stacking data exists.
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This page is educational reference material about compounds studied in research settings. It is not medical advice, and nothing here is a recommendation to buy, possess, or use any compound. Research findings described are from published literature; individual compounds may not be approved for human use. Talk to a licensed clinician about anything that affects your health.