PE-22-28

CognitiveTREK-1 research peptideExperimental

Also known as: Spadin analog, TREK-1 blocker peptide, GVSWGLR

PE-22-28 (also called Spadin analog or TREK-1 blocker peptide) is a TREK-1 research peptide in the Neuromodulator class. PE-22-28 is a shortened analog of spadin, a peptide derived from the propeptide released when sortilin is matured. It blocks TREK-1, a two-pore-domain potassium channel encoded by KCNK2.

Calculate Dose

For research use only.

Key Facts

CAS
1801959-12-5
Molecular Weight (MW)
773.9 g/mol
Half-life
—
FDA status
Not Approved
Evidence level
Insufficient Evidence
Human dose established
No
Administration Route
Not established in humans
Frequency
Not established in humans
Last updated
Nov 7, 2026
Reviewed
Nov 7, 2026
Targets
TREK-1 (KCNK2)

Vendor price snapshot

Each vendor counts once, at the median price per mg of its own listings; the typical range is the middle half of vendors. From public vendor listings collected between Oct 2026 and Nov 2026, so confirm the live price on the vendor site. Peptide Library does not sell peptides.

Vendors listing this peptide
14
Listed offers
16
Median price per mg (peptide vials)
$5.20/mg
Typical $4.40–$6.25/mg

By form

Each form is priced on its own: a price per mg doesn't make a spray or a capsule equivalent to a vial.

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Research summary

Shortened analog of spadin, a peptide derived from sortilin maturation, which blocks the TREK-1 potassium channel. Because mice lacking TREK-1 show a depression-resistant phenotype, the channel became an antidepressant target, and PE-22-28 produces antidepressant-like effects in rodents within days rather than the weeks required by monoamine reuptake inhibitors. Preclinical only, with no human trials, and not FDA-approved.

Research evidence

  • Regulatory review (FDA label)None in reviewed sources
  • Controlled human trialsNone in reviewed sources
  • Early or uncontrolled human studiesNone in reviewed sources
  • Lab & animal studies1 reviewed source
How it works

Each step shows whether the sources Peptide Library has reviewed include that kind of research. Counts are reviewed sources, not every study ever published. Reviews and programme summaries that describe human use are shown as "reported", not as trials, and registered trials without published results are listed but not counted. A higher step means research has progressed further; it does not mean a compound works better or is safer. Compounds whose evidence has not been reviewed yet show "Not reviewed" instead of a guess.

Peptide Library's PE-22-28 profile summarises 5 cited studies listed in the Science section, the compound's regulatory status, and research-protocol parameters reported for it. It is a research reference, not medical advice.

PE-22-28 dosage: no established human dose

PE-22-28 has no established human dosage. No trial of it is registered on ClinicalTrials.gov and no human study is indexed in PubMed. It was designed as a shortened, more stable version of spadin, and the published work is in cells and in mice.

Insufficient Evidence

No established human dosage.

Human clinical evidence: None identified.

Preclinical research: PE-22-28 is a seven amino acid peptide (GVSWGLR) derived from spadin, itself a fragment of the sortilin propeptide, and it acts on the TREK-1 potassium channel. The work published so far is patch-clamp recording in cells and behavioural testing in mice, with weight-based doses given into the abdominal cavity. No human study has given it by any route, so no human dose, route or interval exists.

Animal dosing is not converted into a human dose anywhere on this page. Where research figures appear below, they are reported as studied, not recommended.

Dosage evidence summary for PE-22-28
Human dosing establishedNo
RouteNot established in humans
Evidence levelInsufficient Evidence
Last reviewed2026-11-07

Preclinical and analog research

Not human dosing evidence. Listed for completeness and never extrapolated to a human dose.

Research-reported dosing for PE-22-28, one row per studied regimen
Study / contextPopulationDoseRouteFrequencyDurationOutcome studiedSource
Preclinical — PE 22-28 designed from spadin and tested in mice (2017)Preclinical · Cell and animal studyhTREK-1/HEK cells; mice in behavioural models and mouse cortical neuronsNot stated in the indexed abstract; the reported figure is an in vitro potency (IC50 0.12 nanomolar for TREK-1, against 40-60 nanomolar for spadin)Not stated in the indexed abstract—4 days of sub-chronic treatment in the behavioural testsReduced immobility time in the forced swimming test, shorter latency to eat in the novelty suppressed feeding test, and markers of neurogenesis and synaptogenesis; the authors report activity lasting up to 23 hours against 7 hours for spadinShortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity. Front Pharmacol. 2017.
Preclinical — mini-spadin, described as the short spadin analog, in a mouse stroke model (2019)Preclinical · Animal study of a shortened spadin analogStudied an analog, not PE-22-28 itselfMice with focal ischaemia and post-stroke depression0.03 mcg/kg, then 3 mcg/kg at the later stage (non-human); the abstract calls the peptide mini-spadin and does not name PE 22-28IntraperitonealOnce a day for 7 days after the ischaemia, then once a day 4 days a week—Less body weight loss and dopaminergic degeneration, better motor and cognitive scores, and prevention of post-stroke depression behaviour; the authors report that low doses activated TREK-1 and higher doses inhibited itFirst evidence of protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptides. Neuropharmacology. 2019.

Where sources disagree

  • The mouse doses are in micrograms per kilogram of body weight and were given by intraperitoneal injection, a route not used in people. They do not convert into a human dose.
  • One mouse study reports the opposite effect at a low and a high dose, so a figure taken from that work does not even carry one consistent direction of effect.
  • Spadin, mini-spadin and PE-22-28 are related but different peptides. Results for one are not dosing evidence for another.
  • The search term "PE 22-28" also matches unrelated obstetric and engineering papers in PubMed, which inflates the apparent volume of evidence.

Reconstitution

Common research vial sizes: 8 mg, 10 mg.

Reconstitution arithmetic for PE-22-28
VialBacteriostatic waterConcentrationPer 0.01 mL
10 mg2 mL5 mg/mL50 mcg per 0.01 mL
8 mg2 mL4 mg/mL40 mcg per 0.01 mL

These figures are arithmetic only — they convert a vial and a volume into a concentration. They are not a recommendation to take any dose.

Calculate reconstitution & dose →

Handling & administration

Injection Sites
AbdomenThigh
Timing Notes
Educational catalog only — not medical advice

Sequence & molecular data

Sequence and molecular data for PE-22-28
Amino acid sequenceGVSWGLR
Molecular formulaC35H55N11O9
Molecular weight773.9 g/mol
CAS number1801959-12-5
AppearanceWhite lyophilized powder
FormulationLyophilized Powder

Identifiers link to the public PubChem, FDA Substance Registration (UNII), ChEMBL and DrugBank records for the same entity.

Science

Mechanism of Action

PE-22-28 is a shortened analog of spadin, a peptide derived from the propeptide released when sortilin is matured. It blocks TREK-1, a two-pore-domain potassium channel encoded by KCNK2. TREK-1 activity hyperpolarises neurons and dampens excitability, and mice lacking the channel show a depression-resistant phenotype, which is what made it a target. Blocking TREK-1 increases excitability of serotonergic neurons in the dorsal raphe and promotes hippocampal neurogenesis, producing antidepressant-like effects in rodents within days rather than the weeks required by monoamine reuptake inhibitors. The evidence is preclinical; no human trials have been published.

Origin

Synthetic GVSWGLR analog of spadin.

Targets

TREK-1 (KCNK2)

Research statistics

1 PubMed publications · 0.0% human clinical research · 0 registered trials

Counts of published research through 2026-11-01, not evidence that it works. Publications by year, study types and trials · How publications are counted

Regulatory & research status

PE-22-28 is not an FDA-approved product. It is sold for laboratory research and has no approved medical use.

Regulatory and research status for PE-22-28
FDA statusNot Approved
AvailabilityResearch-Only
WADA (sport)Unknown / Not Listed
Library classificationResearch-Only

How FDA approval, compounding and research-only status differ

Benefits

Depression-model research tool

PE-22-28 side effects

PE-22-28 has no controlled human safety data. The effects below are reported, not established, and absence from the list is not evidence of safety.

Side Effects

  • No established human AE profile

Storage & stability

Lyophilized (freeze-dried) peptide powder is far more stable than the reconstituted solution. Keep sealed vials cold, dry and away from light; long-term storage is typically frozen, with short-term refrigeration for vials in use.

Once reconstituted in bacteriostatic water, keep the solution refrigerated, avoid repeated freeze–thaw cycles and agitation, and label the vial with the reconstitution date and concentration. Discard any solution that turns cloudy or shows particulates.

Degradation rates differ by sequence: peptides containing methionine, cysteine, asparagine or glutamine are more prone to oxidation and deamidation, so shelf life after reconstitution is compound-specific rather than universal.

Read the full guide: how to store peptides before and after reconstitution →

Source: Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharm Res. 2010;27(4):544–575. (PMID 20143256). General guidance for research handling; not product-specific instructions.

PE-22-28: frequently asked questions

What is PE-22-28?

Shortened analog of spadin, a peptide derived from sortilin maturation, which blocks the TREK-1 potassium channel. Because mice lacking TREK-1 show a depression-resistant phenotype, the channel became an antidepressant target, and PE-22-28 produces antidepressant-like effects in rodents within days rather than the weeks required by monoamine reuptake inhibitors. Preclinical only, with no human trials, and not FDA-approved.

How does PE-22-28 work?

PE-22-28 is a shortened analog of spadin, a peptide derived from the propeptide released when sortilin is matured. It blocks TREK-1, a two-pore-domain potassium channel encoded by KCNK2.

Is PE-22-28 FDA approved?

No. PE-22-28 is not approved by the FDA for any indication and is categorised as research-only. It has not been reviewed for safety or efficacy as a medicine, and published research should be read as investigation rather than established use.

What is the amino acid sequence of PE-22-28?

PE-22-28 has the sequence GVSWGLR. Its molecular formula is C35H55N11O9.

What peptides are similar to PE-22-28?

Compounds most often compared with PE-22-28 include Delta Sleep-Inducing Peptide (DSIP), N-Acetyl Selank Amidate, Noopept and Orexin-A. They are grouped by shared mechanism or research area rather than by equivalence, and their regulatory status and evidence base differ.

References

Related research, comparisons & guides

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Compiled by Peptide Library Editorial · Reviewed Aug 30, 2026 · Updated Nov 7, 2026 · Version 2

This PE-22-28 profile is compiled from published literature (5 cited studies linked above), public regulatory records and chemical registries. It describes what research reports; it is not medical advice, and nothing here is a dosing recommendation for humans. Peptide Library does not sell peptides. Editorial policy · How profiles are compiled · Report an error

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