PE-22-28

Areas of active research — not promised effects

Each tag links to other compounds with research into that goal. Research use only: these are areas of study, not human-use claims.

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PE-22-28 has no FDA-approved indication, no active Investigational New Drug (IND) application on public record, and no path to lawful prescribing or dispensing to humans. It was placed on the FDA Section 503A Category-2 bulk drug substances list (effective ~December 2023), prohibiting its use in compounding pharmacies. Unlike DSIP (emideltide) and several other peptides, PE-22-28 was NOT among the 12 peptides removed from Category-2 in April 2026 and is NOT among the seven peptides scheduled for PCAC review on July 23–24, 2026 (docket FDA-2025-N-6895). It therefore remains restricted under Category-2 as of May 2026.

Transparent blend · bci-1.0 · never paid-placement

Primary name

PE-22-28

Origin

PE-22-28 is a seven-amino-acid synthetic peptide corresponding to residues 22–28 of the propeptide PE, from which the endogenous TREK-1-blocking peptide spadin (PE 12-28) is derived. Spadin is a naturally occurring sortilin propeptide fragment; PE-22-28 was rationally truncated from spadin to identify the minimal active sequence, yielding markedly improved in vitro potency and longer in vivo effect duration (PMID 28955242).

Registry IDs

PubChem CID

165437303

CAS

1801959-12-5

InChIKey

CMNBQRXBBJQIOA-YIHYGEMESA-N

InChIKey

CMNBQRXBBJQIOA-YIHYGEMESA-N

Appearance

White to off-white lyophilized powder (vendor-typical)

Solubility

Soluble in water and aqueous buffers at research concentrations; solubility in o…

Sequence not available in current seed.

Stability: As a short linear heptapeptide, PE-22-28 is susceptible to proteolytic degradation; the published study (PMID 28955242) demonstrated that it is more stable in b

Vial sizes

5 mg · 10 mg

Purity grades

≥98% HPLC

Salt forms

Free base (primary)

• GHS hazard class on file
• PPE & spill response
• Disposal guidance
• Not-for-human-consumption posture

How much research exists, and of what maturity — never a verdict on whether it works.

Mechanism of action

• PE-22-28 selectively blocks the TREK-1 two-pore domain potassium channel (K2P), a constitutively active background channel that contributes to neuronal resting membrane potential and dampens serotonergic neurotransmission when overactive
• By inhibiting TREK-1, PE-22-28 reduces hyperpolarization of serotonergic dorsal raphe neurons, thereby enhancing serotonin release and neuronal excitability
• Preclinical evidence from Djillani et al
• (PMID 28955242) demonstrates that PE-22-28 does not meaningfully alter currents through the related K2P channels hTRESK, hTASK-1, TREK-2, or TRAAK, nor does it affect the cardiac hERG channel, indicating a high degree of TREK-1 selectivity

Pharmacokinetics (ADME)

Half-life

Effect duration approximately 14–23 hours in mice after intraperitoneal administration, compared to ~7 hours for the parent peptide spadin; formal plasma half-life not published (PMID 28955242)

PK–PD note: Formal plasma PK characterization (Cmax, AUC, t½, Vd) has not been published in peer-reviewed literature. The extended in vivo effect duration relative to spadin is attributed to resistance to blood-b…

Reading the evidence

• Evidence quality and gaps vary by application — see the cited grades above.
• Indexed-article counts span all evidence tiers, not only completed human trials.
• No first-party human-dosing, efficacy, or benefit claims are made here.

Key reviews & evidence-gap sources

• Djillani A, Pietri M, Mazella J, Heurteaux C, Borsotto M. Fighting against depression with TREK-1 blockers: Past and future. A focus on spadin. Pharmacol Ther. 2019 Feb;194:185-198. (Review, PMID 30291907) — Peer-reviewed review in Pharmacology & Therapeutics covering the spadin/TREK-1 blocker class, including PE-22-28 as a shortened spadin analog. Indexed for MEDLINE; pubtype includes 'Review'.
• Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M. Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity. Front Pharmacol. 2017 Sep 12;8:643. (Primary research, PMID 28955242) — Primary original article (not a review) — the sole PubMed-indexed PE-22-28-specific publication. Includes in vitro hTREK-1/HEK patch-clamp (IC50 0.12 nM), mouse behavioral models (forced swim test, novelty suppressed feeding), neurogenesis and synaptogenesis assays.

No registered human trials found for this compound.

Status

No registered trials found

Summary (literature)

No human safety or tolerability data for PE-22-28 exist; no clinical trials have been registered or completed. In the rodent studies of Djillani et al. (PMID 28955242), PE-22-28 and its analogs were reported to be devoid of detectable effects on cardiac hERG channels, suggesting …

WADA status

Not specifically listed on the WADA 2026 Prohibited List. PE-22-28 does not fall under currently enumerated categories of prohibited peptide hormones, growth fa…

Dominant research route: Intraperitoneal (IP) injection in mice — the route used in the primary Djillani et al. 2017 behavioral and neurogenesis studies.

Primary in vivo route in C57BL/6J mice at 3.2–4.0 µg/kg (forced swim test, novelty-suppressed feeding, 4-day sub-chronic neurogenesis protocol)

Bioavailability: Intraperitoneal injection was the principal route used in the Djillani et al. 2017 mouse behavioral and neurogenesis studies; antidepressant-like effects and 4-day neurogenesis were demonstrated via this route.

Dose ~25-fold lower than the 100 µg/kg required for parent spadin; duration of action extended to ~23 h vs 7 h for spadin. No human PK data exist.

Listed among effective administration routes for spadin and its analogs (including PE-22-28) in a 2019 Pharmacology & Therapeutics review; original spadin work (Mazella 2010) demonstrated IV antidepressant effects in mice

Bioavailability: Review states spadin and its analogs are effective regardless of route, including intravenous; no dedicated PE-22-28 IV PK study identified.

Route efficacy asserted in review literature; specific PE-22-28 IV pharmacokinetic parameters not separately reported.

Cited as an effective administration route for spadin/analogs in the 2019 review; community/secondary sources describe SC as a route used in animal research

Bioavailability: Review indicates spadin analogs are active via subcutaneous administration; no isolated PE-22-28 SC bioavailability figure located.

Listed alongside IV, IP, ICV, and per os as routes over which spadin analogs retain efficacy.

Listed as an effective route for spadin and analogs in the 2019 Pharmacology & Therapeutics review; no dedicated PE-22-28 oral absorption/bioavailability study identified

Bioavailability: Review asserts spadin analogs are effective 'per os'; however, a secondary clinical source notes PE-22-28 'requires parenteral or intranasal administration due to poor oral bioavailability.' No quantitative oral bioavailability value is published.

Oral-stability (in-solution) data exist but are distinct from oral absorption; the review's per-os efficacy claim refers to spadin-family activity, not a characterized PE-22-28 oral PK profile.

No peer-reviewed intranasal PE-22-28 study located; discussed only in secondary/community sources as a theoretical CNS-delivery route

Bioavailability: Community/secondary sources describe intranasal as a preferred route for CNS delivery, but note bioavailability is 'variable and technique-dependent'; no controlled intranasal PK data published.

Intranasal use is community-reported and not supported by primary preclinical or clinical PE-22-28 data; included as Layer B aggregate community route only.

Animal & human figures are kept visibly separate so studied animal doses are never misread as human guidance.

Sorted A–Z by vendor — never by price

Weekly median $/mg from the live vendor crawl.

Researched storefront prices, bucketed

p25 $4.80 · median $6.00 · p75 $6.88 · 10 researched vendors

Legit, COA-backed band: $4.40–$8.09/mg.

Value rule: don't just buy the cheapest — a price under $3/mg is a red flag. Pair price with COA and independent-test grade.

Estimated cost of research (10 mg)

Vial (best researched price)

$30

Bacteriostatic water (generic estimate)

$6

Syringes / supplies (generic estimate)

$12

What each test proves — general guidance, plus this compound's researched purity data

Purity on the current market (researched)

Vendor-stated purity: ≥99% by HPLC (Paramount Peptides, BiotechPeptides); ≥98% (Cayman Chemical, research-grade supplier). No independent third-party purity results specific to PE-22-28 were located in the sources retrieved.

Independent labs cited for this compound

No FDA recalls, seizures, warning letters, or criminal enforcement actions naming PE-22-28 specifically were found in the sources retrieved. Import Alert 66-41 applies to unapproved new drug peptides generally but PE-22-28 is not named on a published Red List in the sources reviewed.

Buyer red-flag checklist

• Not FDA-approved for any use; no IND, no completed Phase 1 human safety study, no human pharmacokinetic data (superpower.com).
• No manufacturing oversight, no required identity testing, no purity specification, and no validated human dose-response for gray-market PE-22-28 products (superpower.com).
• Independent testing of gray-market peptide products has documented contamination, incorrect concentrations, and misidentified compounds in a significant fraction of samples (superpower.com).
• Aggregate peptide-market testing finds ~1/3 of products fail basic quality checks (identity, purity <98%, or quantity mismatch) (Finnrick via The Guardian, Apr 2026).
• An RUO ('research use only') label does not create an importation exemption under FDA Import Alert 66-41 (chemverify.com).
• Vendors self-report purity (≥99% / ≥98%) without universal independent verification; no PE-22-28-specific third-party COA was located in retrieved sources.

GMP vs research-grade: the chemistry (SPPS + HPLC + MS) is identical — the difference is the quality system.

Underdosing / mislabeling: No PE-22-28-specific underdosing prevalence was found. Independent aggregate peptide-market testing (Finnrick, reported by The Guardian, Apr 2026) found ~1/3 of thousands of analyzed peptide products failed basic quality checks (identity, purity below 98% threshold, or quantity mismatch), a proportion broadly unchanged over 12–14 months. This is a market-wide figure, not PE-22-28-specific.

• Detention Without Physical Examination of Unapproved New Drugs Promoted In The U.S. Authorizes FDA field divisions to detain qualifying peptide imports without opening/testing each parcel; an RUO label does not by itself exempt a product. Revised 19 May 2026. PE-22-28 is not named on a retrieved Red List; the alert applies to the unapproved-new-drug peptide class generally.66-41
• An RUO label is not an import exemption — CBP judges actual intended use.
• Lyophilized powder is ambient-stable in transit; temperature control needed for > 7-day transit.
• US-warehouse vendors dodge import scrutiny — they cost more but ship more reliably.

Every item dated & sourced

Prohibited under S0 (Non-Approved Substances) on the 2026 WADA Prohibited List (effective January 1, 2026). PE-22-28 has no approval from any global health authority and thus meets the S0 criteria. No Therapeutic Use Exemption (TUE) pathway is available for S0 substances without regulatory approval.

No granted patents identified in current seed. Composition-of-matter coverage is limited given the peptide's synthetic origin.

• IACUC / IRB research context
• RUO buyer responsibilities & documentation
• Veterinary / alternative-use where lawful
• Jurisdiction-aware "who may lawfully obtain"

What people discuss

Reported concerns — discussion, not established effects

Reading caveats

• small-n self-report
• enthusiasm / early-adopter bias
• vendor-affiliated content present
• no completed human RCT cited in discussion

Manually researched from reddit, youtube— theme weights are research estimates, not live counts; aggregated & de-identified. No individual posts, quotes, or usernames are ever shown.

Relative research / market volume — populated once the activity stream is wired

Inline tooltips for lyophilized, RUO, EU/mg, SPPS, 503A and more.

Toggle plain-language ↔ scientific in the header.

• How to read a COA
• Free base vs acetate
• Understanding evidence grades

Synthetic heptapeptide derived from spadin that selectively inhibits the TREK-1 potassium channel; studied preclinically as a fast-acting antidepressant and neurogenesis inducer. Approximately 1 articles are indexed (literature last scanned 2026-05-29). US regulatory status: Research Use Only — not approved; remains on FDA Category-2 'do not compound' list. Research use only.

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