Overview
Overview
PE-22-28 is a synthetic heptapeptide (sequence: GVSWGLR) derived from the sortilin propeptide, engineered as a potent and selective antagonist of TREK-1 potassium channels[4]. Preclinical studies demonstrate rapid antidepressant-like effects, enhanced neurogenesis, and neuroprotection with a favorable safety profile showing no cardiac or metabolic side effects[2][3]. This educational protocol presents a once-daily subcutaneous approach with gradual titration. Reconstitute: Add 3.0 mL bacteriost
- Category
- Cognitive
- Routes
- subcutaneous
Mechanism
PE-22-28
Mechanism of action
Mechanism of action
PE-22-28 functions as a potent and selective antagonist of TREK-1 (KCNK2) two-pore domain potassium channels [2] . By blocking TREK-1, it depolarizes neurons and enhances excitability, leading to increased firing of serotonergic neurons and elevated monoamine neurotransmission [2] . This mechanism produces rapid antidepressant-like effects in preclinical models—within 4 days, PE-22-28 significantly increases hippocampal neurogenesis and synaptogenesis markers, changes typically requiring weeks with conventional antidepressants [4] . The peptide also activates CaMKII/CREB pathways that promote neuronal survival and plasticity [6] . PE-22-28 represents a shortened, optimized analog of spadin with superior potency (IC 50 ~0.12 nM versus 40–60 nM for spadin) and longer duration of action (~23 hours versus ~7 hours) [4] . Notably, research also demonstrates neuroprotective effects in stroke models through biphasic dosing that leverages both TREK-1 activation at ultra-low doses and inhibition at standard doses [5] .
Key research findings
- 01
PE-22-28 is a synthetic peptide, a shortened analog of spadin, which is derived from the propeptide region of sortilin (neurotensin receptor-3); analogs were developed to retain activity with improved stability (in vitro / animal model).
- 02
Mechanistic work attributes effects to inhibition of the TREK-1 (TWIK-related K+ channel 1) two-pore-domain potassium channel, a target studied in mood-related neurophysiology research (in vitro / animal model).
- 03
In rodent models, spadin and PE-22-28 have been studied for antidepressant-like behavioral profiles and for markers of hippocampal neurogenesis and synaptogenesis (animal model).
- 04
The research is preclinical; no established human clinical trials specific to PE-22-28 were identified (evidence: preclinical only).
Primary source: PE-22-28 has a small, preclinical research base built on the spadin/TREK-1 line of work (characterized by Mazella and colleagues in France), consisting mainly of rodent behavioral and neurobiological studies. Human clinical data specific to PE-22-28 are essentially absent, so it should be regarded as an early-stage research compound.
Researched Effects
Researched benefits
Areas of active research and investigation. Results may vary and are based on preclinical or early clinical data.
& Observed Safety Profile
Protocol Reference
Protocol reference
Commonly cited research range: 50–200 mcg, daily.
Reference figures reported in the research literature — not a dosing recommendation. For interactive vial math and scheduling, see the Calculator and Schedule tabs.
Cited protocol & reconstitution guide
Source-backed reference fields by phase, including any volume fields authored in the cited guide.
Weeks 1–2
50 µg
Weeks 3–4
100 µg
Weeks 5–8
100 µg
Weeks 9–12 (Optional)
150 µg
Weeks 13–16 (Optional)
200 µg
| Phase | Reference amount | Units / volume |
|---|---|---|
| Weeks 1–2 | 50 µg | 1.5 units (0.015 mL) |
| Weeks 3–4 | 100 µg | 3 units (0.03 mL) |
| Weeks 5–8 | 100 µg | 3 units (0.03 mL) |
| Weeks 9–12 (Optional) | 150 µg | 4.5 units (0.045 mL) |
| Weeks 13–16 (Optional) | 200 µg | 6 units (0.06 mL) |
Storage & Handling
Storage requirements(typical for most peptides)
Can be stored for extended periods. Protect from moisture.
Store in refrigerator door. Never freeze after reconstitution.
Label vials with reconstitution date. Discard if cloudy.
Reconstitution steps
- 01🌡️Draw 3.0 mL bacteriostatic water with a sterile syringe.
- 02🧴Inject slowly down the vial wall; avoid foaming.
- 03💉Gently swirl/roll until dissolved (do not shake).
- 04💧Label and refrigerate at 2–8 °C (35.6–46.4 °F), protected from light.
- 05🔄Important: This guide is for educational purposes only and is not medical advice. For research use only. Not for human consumption.
Additional storage notes
Store at −20 °C (−4 °F) in dry, dark conditions; minimize moisture exposure.
Refrigerate at 2–8 °C (35.6–46.4 °F); use within 4 weeks for optimal potency.
Allow vials to reach room temperature before opening to reduce condensation; protect from light.
Replace with fresh vial every 4 weeks even if peptide remains; bacteriostatic water sterility is guaranteed for 28 days after first puncture [10] .
Clinical Evidence
Clinical evidence
Preclinical rodent studies report rapid antidepressant-like and neurogenic activity via TREK-1 blockade; human data are not established.
PE-22-28 has a small, preclinical research base built on the spadin/TREK-1 line of work (characterized by Mazella and colleagues in France), consisting mainly of rodent behavioral and neurobiological studies. Human clinical data specific to PE-22-28 are essentially absent, so it should be regarded as an early-stage research compound.
- 01PE-22-28 is a synthetic peptide, a shortened analog of spadin, which is derived from the propeptide region of sortilin (neurotensin receptor-3); analogs were developed to retain activity with improved stability (in vitro / animal model).
- 02Mechanistic work attributes effects to inhibition of the TREK-1 (TWIK-related K+ channel 1) two-pore-domain potassium channel, a target studied in mood-related neurophysiology research (in vitro / animal model).
- 03In rodent models, spadin and PE-22-28 have been studied for antidepressant-like behavioral profiles and for markers of hippocampal neurogenesis and synaptogenesis (animal model).
- 04The research is preclinical; no established human clinical trials specific to PE-22-28 were identified (evidence: preclinical only).
Evidence maturity varies by compound; much peptide research is preclinical (in vitro or animal-model). Where human data are limited, findings should be read as research observations, not clinical conclusions.
References
Literature references
Published research articles and sources related to PE-22-28.
- 01Pure Lab Peptides — PE-22-28 (10 mg) product page (research-grade peptide, quality documentation) View Source
- 02PLoS Biology (2010) — Mazella et al.: Spadin, a sortilin-derived peptide targeting TREK-1 channels; novel antidepressant mechanism View Sourceet al. (2010)
- 03Neuropharmacology (2012) — Moha Ou Maati et al.: Spadin as antidepressant; absence of TREK-1-related side effects View Sourceet al. (2012)
- 04Frontiers in Pharmacology (2017) — Djillani et al.: Shortened spadin analogs (PE-22-28); superior TREK-1 inhibition, in vivo stability, antidepressant activity View Sourceet al. (2017)
- 05Neuropharmacology (2019) — Pietri et al.: Protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptides View Sourceet al. (2019)
- 06Pharmacological Research (2021) — Daziano et al.: Sortilin-derived peptides promote pancreatic beta-cell survival through CREB signaling pathway View Sourceet al. (2021)
- 07International Journal of Molecular Sciences (2022) — Chang et al.: Potential of heterogeneous compounds as antidepressants; narrative review including TREK-1 modulators View Sourceet al. (2022)
- 08CDC — Vaccine administration: subcutaneous injection instruction guide (technique, angle, no aspiration) View Source
- 09CDC — 4 Ways to Take Insulin; section on injection site rotation and subcutaneous technique View Source
- 10CDC Pink Book — General best practice guidelines: vaccine administration; multi-dose vial 28-day sterility rule View Source
Research Considerations
Research considerations
Research Use Only - not for human or veterinary therapeutic use. Evidence is strictly preclinical (cell and/or animal models); it is a research compound, not a therapy, and has not been evaluated for human safety. Consult a licensed healthcare professional for any clinical decisions.
Factors noted in the research literature; not patient-specific medical advice.
Regulatory Status
Regulatory status
RUO
Comparisons
Comparisons
| Compound | Mechanism | Route | Status |
|---|---|---|---|
| PE-22-28this | A synthetic heptapeptide (GVSWGLR) derived from the sortilin propeptide that acts as a selective antagonist of TREK-1 potassium channels, a mechanism studied for mood regulation and neuroplasticity. | subcutaneous | Investigational / RUO |
| Pinealon | A synthetic tripeptide bioregulator (Glu-Asp-Arg) studied for cell-penetrating, gene-regulatory activity in neural tissue, with proposed antioxidant and neuroprotective effects. | subcutaneous | Investigational / RUO |
| Selank | Modulates GABA and serotonin systems. Increases BDNF. Provides anxiolytic effects without sedation or cognitive impairment. | nasal, subcutaneous | Investigational / RUO |
| Semax | Increases BDNF expression, enhances dopamine and serotonin metabolism. Provides neuroprotection and cognitive enhancement. | nasal, subcutaneous | Investigational / RUO |
| Cerebrolysin | A porcine brain-derived preparation of low-molecular-weight neuropeptides and free amino acids studied for neurotrophic activity supporting neuronal survival, synaptic plasticity, and modulation of neuroinflammation. | subcutaneous | Investigational / RUO |
| PEG MGF | A pegylated form of mechano growth factor designed for extended stability and systemic half-life; the C-terminal E-peptide is studied for satellite-cell activation and muscle repair. | subcutaneous | Investigational / RUO |
| PNC-27 | A synthetic peptide combining an HDM-2-binding domain with a membrane-penetrating sequence, studied for selective membrane disruption of cancer cells displaying surface HDM-2. | subcutaneous | Investigational / RUO |
Attributes shown for research comparison only; not a statement of efficacy or therapeutic equivalence.
FAQ
Frequently asked questions
PE-22-28 is a synthetic peptide analog of spadin, which is derived from the propeptide of sortilin. It is studied as a TREK-1 potassium channel modulator and supplied for Research Use Only.
Research describes blockade of the TREK-1 (TWIK-related potassium channel 1), a target studied in the context of mood-related neurophysiology. This is a research-stage mechanism.
The evidence is preclinical, based mainly on rodent studies of behavior and neurogenesis. No established human clinical trials specific to PE-22-28 were identified, so conclusions are early-stage.
PE-22-28 is a shortened analog of spadin designed to retain TREK-1 activity with greater stability. Both originate from the same research program.
Reported research ranges and routes vary across preclinical studies and are not standardized for human use. PeptiJournal does not provide dosing instructions; see the protocol reference. This is not medical advice.
Lyophilized peptide is generally stored cold, dry, and dark; reconstituted solution is typically refrigerated and used within a limited window. Follow the certificate of analysis and protocol reference.
PE-22-28 is not an approved drug and is handled strictly as a Research Use Only material.
Research-use notice
Research Use Only. This educational content and calculation support is intended for private research documentation. It does not provide medical advice, human-use directions, or claims of safety or effectiveness.