Evidence Snapshot
What this grade covers
A for sequence identity; B/C for direct TREK-1 cell pharmacology and mouse findings; E for human antidepressant, anxiolytic, neuroregenerative, cognitive, safety, approval, or dosing claims.
Regulatory Context
Experimental research compound; no FDA-approved product and no verified administered-human clinical trial were identified.
Research Takeaway
PE-22-28, also called mini-spadin, is a seven-amino-acid shortened spadin-derived peptide and is distinct from parent spadin/PE12-28, PE1-44, G/A-PE-22-28, biotinylated analogs, and other TREK-1-modulating compounds.
Evidence boundary: Parent-spadin and derivative data transfer only when PE-22-28 itself was directly tested.
See all 6 evidence claims →Quick Summary
PE-22-28 is a seven-amino-acid fragment derived from the spadin research program and studied as a TREK-1 potassium-channel inhibitor. The evidence located is preclinical only.
Mechanism & Research Overview
PE-22-28 was designed as a shortened spadin analog. Experimental work reports potent TREK-1 inhibition and antidepressant-like, neurogenesis, and synaptogenesis signals in mice and cultured neurons.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
PE-22-28, also called mini-spadin, is a seven-amino-acid shortened spadin-derived peptide and is distinct from parent spadin/PE12-28, PE1-44, G/A-PE-22-28, biotinylated analogs, and other TREK-1-modulating compounds.
Does not establish
Evidence boundary: Parent-spadin and derivative data transfer only when PE-22-28 itself was directly tested.
Supported
In vitro, PE-22-28 potently inhibited the TREK-1 potassium channel and showed greater apparent potency than parent spadin in the published experimental system.
Does not establish
Evidence boundary: In-vitro channel potency does not establish antidepressant efficacy or safety in humans.
Supported
PE-22-28 produced antidepressant-like effects in multiple mouse behavioral paradigms in the foundational shortened-spadin study.
Does not establish
Evidence boundary: Animal behavioral tests model selected antidepressant-like responses and are not equivalent to treatment of major depressive disorder in humans.
Supported
PE-22-28 increased experimental markers associated with neurogenesis and synaptogenesis, including hippocampal BrdU-positive cells and PSD-95-related measures in mouse neuronal systems.
Does not establish
Evidence boundary: These laboratory markers do not establish clinically meaningful neurogenesis, cognitive improvement, or psychiatric benefit in humans.
Supported
This package identifies no controlled human PE-22-28 efficacy or safety trial; the evidence base remains preclinical.
Does not establish
Evidence boundary: Published work on parent spadin or modified PE-22-28 derivatives cannot fill the absence of exact-compound human trials.
Supported
PE-22-28 should remain presented as an experimental TREK-1-targeting research peptide rather than an established antidepressant.
Does not establish
Evidence boundary: Promising animal antidepressant-like activity is insufficient for a human therapeutic claim.
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
No human pharmacokinetic, safety, or efficacy data were verified.Safety Consideration
TREK-1 participates in multiple neural and peripheral functions, so selective benefit cannot be assumed.Safety Consideration
Online claims that PE-22-28 is a BDNF mimetic or TrkB agonist conflict with the primary literature and should be rejected.Safety Consideration
CNS overexcitation, agitation, insomnia, anxiety, mood destabilization, mania, and suicidality are theoretical concerns given TREK-1's excitability role. Seizure-threshold, pain/anesthesia/mechanosensation, and cardiovascular/vascular effects follow from broader TREK-1 physiology. Brain delivery/bioavailability, off-target ion-channel activity, immune/reproductive/developmental effects, aggregation, impurities, sequence errors, sterility, endotoxin risk, and interactions with antidepressants, stimulants, sedatives, anticonvulsants, or anesthetics are all unstudied in humans.
Research Areas Being Studied
Research areas discussed on this page reflect the Cognitive / Neuro category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
No Human Study Findings Listed Yet
See preclinical, regulatory, and review sources below.
Study Tables by Evidence Type
Human Studies & Clinical Data
No Human Studies & Clinical Data Listed Yet
This section will be updated as sources are added.
Animal / Cell / Preclinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Full Text: Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity | Full-text version of the direct 2017 PE-22-28 research program: inhibition of human TREK-1 current in transfected cells with apparent potency exceeding parent spadin, mouse forced-swim/learned-helplessness/corticosterone/novelty-suppressed-feeding findings, increased BrdU-positive hippocampal cells after short mouse treatment, increased PSD-95 in cultured mouse cortical neurons, and longer measured activity than spadin in the tested mouse paradigm. All direct efficacy evidence remains preclinical and concentrated in one research group. | ||||
| Spadin Regulation of Synaptogenesis | Reports parent-compound spadin effects on synaptogenesis. Kept as an explicit parent-compound boundary source: findings about spadin do not establish the same effect for the distinct, shorter PE-22-28 fragment. | ||||
| Spadin, a Sortilin-Derived Peptide Targeting Rodent TREK-1 Channels | Original discovery paper for spadin, the sortilin-derived parent peptide from which PE-22-28 (residues 22-28) is fragmented, targeting rodent TREK-1 channels. Parent-compound context: evidence about spadin itself cannot automatically be assigned to the shorter PE-22-28 fragment. |
Regulatory Documents & Official Trial Registries
No Regulatory Documents & Official Trial Registries Listed Yet
This section will be updated as sources are added.
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational information only. This page summarizes published and official research and does not provide medical advice, a recommendation, or instructions for human use.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated 2026-07-30.
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