← All compounds · evidence tier first, by design
| Use | E1 | E2 | E3 | E4 | E5 | E6 | E7 | E8 |
|---|---|---|---|---|---|---|---|---|
| E6 Depression | E6 |
PE-22-28
GVSWGLR
Residues 22-28 of the mouse sortilin propeptide (PE). Derived from the published spadin sequence (PE 12-28, APLPRWSGPIGVSWGLR) and the statement that glycine occupies position 22; the free peptide's terminal groups were not verified.
Also: PE 22-28, Spadin analogue PE 22-28
A seven-amino-acid peptide cut down from spadin, a fragment of the propeptide released when the sorting protein sortilin matures. It was designed in a French laboratory as a blocker of the TREK-1 potassium channel and tested for antidepressant-like activity in mice. It is sold online as a research chemical with claims for depression, mood and cognition. No study in humans was identified and no approved medicine contains it.
- US C gray market
- EU C gray market
- UK ? not verified
- CA C gray market
- AU ? not verified
- JP ? not verified
- CN ? not verified
01Regulatory status, by jurisdiction
| Jurisdiction | Status | Detail and primary source |
|---|---|---|
| US | Not approved | No FDA-approved application: openFDA Drugs@FDA returns no application with a PE-22-28 active ingredient (query: products.active_ingredients.name:"PE-22-28"). PE-22-28 does not appear in Category 1, 2 or 3 of FDA's 503A bulk drug substances nomination list (updated 14 May 2026). openFDA states its data are unvalidated.“No matches found!”openFDA Drugs@FDA API (FDA) · retrieved 2026-10-10 |
| EU | Not approved | No product containing PE-22-28 or spadin appears in EMA's downloadable medicines dataset (generated 10 Oct 2026), which covers centrally authorised medicines, refusals and withdrawn applications. National authorisations were not checked individually.“This includes information on marketing authorisations of centrally authorised medicines and post-authorisation procedures.”Download medicine data | European Medicines Agency (EMA) · retrieved 2026-10-10 |
| CA | Not approved | A query of Health Canada's Drug Product Database API for the active ingredient spadin returned no products on the retrieval date; PE-22-28 has no ingredient name under which it could be listed.“Search by drug identification number”Drug Product Database online query · retrieved 2026-10-10 |
| UK AU JP CN | Not yet verified from a primary source. No status is shown rather than an unsourced one. | |
Sport (WADA): Prohibited · class S0. PE-22-28 is not named on the 2026 Prohibited List; as a substance with no governmental approval for human use identified, it falls under class S0. “Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use” WADA source
02What the human evidence shows
Depression
No human trial of any design has been published for this use.
Efficacy data are from mice only. In the 2017 report that introduced it, PE 22-28 reduced immobility in the forced swim test, shortened escape latency in a learned-helplessness test and reduced feeding latency in a novelty-suppressed feeding test, including in a corticosterone-induced depression model, with a longer-lasting effect than its parent peptide spadin. These are behavioural screening tests in mice; no human study of mood, depression or any other outcome was identified.
- [1] Inhibited TREK-1 channels in a human cell line and reduced depression-like behaviour in mouse forced-swim, learned-helplessness and novelty-suppressed feeding tests
- [2] The parent peptide spadin blocked TREK-1 and reduced depression-like behaviour in mice (spadin, not PE 22-28)
Registered-study counts: ClinicalTrials.gov intervention search “PE-22-28”, fetched 2026-10-10. Registered studies include trials of other uses; the gap between registered and reported is itself a finding.
03Safety signals
There are no adequate human safety data. The absence of reported harm is not evidence of safety.
04What is unknown
- No human data of any kind were identified: no pharmacokinetic, safety or efficacy study in people
- Whether TREK-1 blockade in humans affects heart rhythm, pain sensitivity or seizure threshold is unstudied for this peptide; TREK-1 is expressed in heart and nerve tissue
- Mouse behavioural tests such as the forced swim test screen for antidepressant-like activity and do not establish an effect on human depression
- Identity, purity and terminal modifications of material sold as PE-22-28 are uncharacterised
- Status in the UK, Australia, Japan and China was not verified from regulator sources for this record
05Product quality
No independent purity results have been published for this compound yet. The purity programme will publish full methods and vendor-named results, passes and failures, once its protocol has had legal review.
06Citations
- Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity (2017). doi:10.3389/fphar.2017.00643
- Spadin, a Sortilin-Derived Peptide, Targeting Rodent TREK-1 Channels: A New Concept in the Antidepressant Drug Design (2010). doi:10.1371/journal.pbio.1000355
Every DOI is resolved against Crossref and every NCT number against ClinicalTrials.gov, title for title, before publication. Regulatory sources are cited inline above with a verbatim quote and retrieval date.
07Mechanism
PE-22-28 blocks the TREK-1 two-pore-domain potassium channel; in cultured cells expressing human TREK-1 it inhibited channel currents with higher potency than spadin.
Mechanism is placed last on purpose: a plausible mechanism is not evidence that a compound works in people.
Reviewed by OSMF research team (AI-assisted, source-verified) on 2026-10-10. Found an error? It goes in the corrections log: report it.