PE-22-28 is a synthetic seven-residue peptide, Gly-Val-Ser-Trp-Gly-Leu-Arg, corresponding to residues 22 through 28 of the 44-amino-acid human sortilin propeptide, and the originating laboratory also reports it under the name mini-spadin. It was designed from the blood degradation products of spadin, the seventeen-residue parent fragment, and is studied in vitro and in preclinical rodent models as a modulator of TREK-1, the two-pore-domain potassium channel encoded by KCNK2.
Researchers meet this molecule as PE 22-28, PE22-28, and mini-spadin, and search for it as PE 22 28 peptide; the primary literature uses the forms unevenly. This guide closes the identity chain first, then separates direct PE-22-28 experiments from parent-spadin findings, independent replication, human biomarker research, and untested assumptions.
Research boundary: PE-22-28 is discussed as a research-grade chemical reagent for in-vitro and preclinical research. It has no marketing authorization and is not for human consumption. Animal study parameters are experimental details, not instructions, and the reported action-duration figure is not a half-life or dosing interval.
- PE-22-28 is the defined heptapeptide GVSWGLR, CAS 1801959-12-5, derived from the human sortilin propeptide.
- PE 22-28 and mini-spadin identify the same seven-residue research peptide in the originating literature.
- Direct electrophysiology reports inhibition in an engineered hTREK-1/HEK system, while a separate study reports activation at lower tested doses and inhibition at higher ones.
- No unaffiliated laboratory has directly tested PE-22-28, no administered-human study exists, and no registered clinical trial was located.
What Is PE-22-28?
PE-22-28 is a synthetic linear seven-residue peptide. PubChem CID 165437303 resolves the sequence as Gly-Val-Ser-Trp-Gly-Leu-Arg, abbreviated GVSWGLR, with a free N-terminal amine and free C-terminal acid in the registry structure. The same record gives CAS 1801959-12-5, formula C35H55N11O9, average molecular weight 773.9 g/mol, and monoisotopic mass 773.41842237.
| Field | Record | Interpretation boundary |
|---|---|---|
| Sequence | GVSWGLR; seven residues | Defines the chain, not its manufactured salt form, purity, stability, or activity. |
| Parent lineage | Human SORT1 propeptide positions 22–28; also called mini-spadin | The 44-residue propeptide count is human-specific; the mouse propeptide is 42 residues. |
| Registry | PubChem CID 165437303; CAS 1801959-12-5 | A registry mapping is not a development code or regulatory authorization. |
| Formula and mass | C35H55N11O9; 773.9 g/mol average | Computed free-peptide values, not a current-lot measurement. |
No INN, USAN, sponsor development code, human pharmacokinetic half-life, or marketing authorization was located. Catalog strings such as HY-P3581 or vendor inventory codes are not development codes.
Where PE 22-28 Comes From: Sortilin, the Propeptide, and Spadin
Human sortilin—also called neurotensin receptor-3, NTSR3—is encoded by SORT1. UniProt Q99523 marks a 44-residue propeptide at positions 34–77. Spadin is the 17-residue fragment corresponding to propeptide positions 12–28. Mazella et al. (2010) introduced spadin as a sortilin-derived peptide studied against rodent TREK-1 channels.
Djillani et al. (2017) reported designing a seven-amino-acid peptide from spadin blood-degradation products: PE 22-28. Mazella, Borsotto, and Heurteaux (2018) provides the essential alias bridge, calling sequence 22–28 “mini-spadin.” Its reported 40–350-fold affinity improvement belongs collectively to mini-spadin and modified analogs, not to PE-22-28 alone.
The heptapeptide GVSWGLR is conserved between the human and mouse sortilin propeptides, but the longer parent segments are not identical. The human propeptide has 44 residues; the mouse propeptide has 42. Human and mouse spadin also differ outside positions 22–28. Conservation of the seven-residue sequence reduces a chemical-identity gap, not the physiological species gap.
How the TREK-1 Mechanism Is Characterized
TREK-1 is the two-pore-domain potassium channel K2P2.1 encoded by KCNK2. Moha ou Maati et al. (2011) developed the human TREK-1/HEK screening line used in this research program. In that engineered system, Djillani 2017 reported an IC50 of 0.12 nM for PE 22-28 compared with 40–60 nM for spadin. That is assay potency in a heterologous cell line, not tissue potency, animal exposure, or a dose.
The “blocker” label is incomplete. Pietri et al. (2019) reported a biphasic action for mini-spadin: channel activity increased at lower tested doses and decreased at higher tested doses. The same paper studied mouse focal ischemia and post-stroke behavioral outcomes. The direction reversal means concentration and assay conditions are part of the mechanism claim, not optional detail.
What the Originating Research Group Demonstrated
| Paper | Material and model | What can be said |
|---|---|---|
| Djillani 2017 | PE 22-28 and modified analogs; hTREK-1/HEK cells and mice | Direct channel inhibition, mouse behavioral findings, neurogenesis and synaptogenesis claims with collective attribution. “Up to 23 h” spans the peptide-and-analog set and is not a PK half-life. |
| Pietri 2019 | Mini-spadin; mouse focal ischemia | Biphasic channel action and model-specific stroke-recovery observations; no human implication. |
| Daziano 2021 | PE and derivatives; beta cells in vitro | Collective beta-cell survival signaling; mini-spadin-specific proliferation. The model is peripheral and cell-based. |
| Djillani 2019 (Pharmacology & Therapeutics) and Djillani 2019 (Frontiers in Pharmacology) | Reviews from the originating network | Useful lineage and field summaries, not independent replication or new experimental outcomes. |
Several frequently repeated findings belong to the 17-residue parent spadin rather than PE-22-28: MAPK/PI3K signaling, BDNF induction, serotonergic effects, and broader channel or safety screens. Examples include spadin synaptogenesis work (Devader et al. 2015), 5-HT4/mGluR2 interactions (Moha ou Maati et al. 2016), retro-inverso analog experiments (Veyssiere et al. 2015), and reported absence of selected TREK-1-knockout-associated effects (Moha Ou Maati et al. 2012). The K2P selectivity panel usually quoted for this family—TREK-2, TRAAK, TASK, and TRESK—was screened against spadin, not against the heptapeptide; no equivalent named-channel panel for PE-22-28 was located in the frozen search. These records remain adjacent context, not direct PE-22-28 proof.
Where the Literature Disagrees: Replication, Channel Identity, and Dose Direction
No unaffiliated laboratory has directly replicated PE-22-28. Two independent groups instead tested parent spadin and reached different system-level conclusions. Ma and Lewis (2020) expressed murine TREK-1 and TREK-2 in Xenopus oocytes. Basal currents were insensitive to spadin, although the peptide narrowly antagonized arachidonic-acid activation. That is not a failed PE-22-28 replication; it is a parent-spadin result in a specific heterologous system.
Bae et al. (2020) reported that spadin dramatically reduced astrocytic passive conductance in brain slices, and gene-silencing experiments in cultured astrocytes and hippocampal astrocytes assigned that current to TWIK-1/TREK-1 heterodimeric channels. Ma and Lewis found no basal sensitivity; Bae and colleagues found a substantial spadin-sensitive current. Together with the biphasic mini-spadin finding, the record supports “unsettled across systems,” not “refuted” and not a simple, universal TREK-1-blocker claim.
What Human Data Exists—and What It Is Not
No study in the verified source set administered PE-22-28 to people. Human papers measured the endogenous sortilin-derived propeptide as a biomarker. Devader et al. (2017) reported lower serum propeptide concentrations in a major-depressive-disorder cohort and changes during conventional treatment. Roulot et al. (2018) found no difference between a treatment-resistant cohort and controls, and separately reported that serum propeptide rose about a month after electroconvulsive therapy, with the increase reaching significance only in responders. The populations and designs differ, so the pair is not a clean replication.
Mazella et al. (2025) assessed serum propeptide concentrations in the STROKDEM chronic-stroke cohort (NCT01330160), an observational study in which no participant received PE-22-28 or spadin. These are biomarker studies of endogenous material, not trials of the seven-residue reagent. ClinicalTrials.gov searches for spadin and PE 22-28 returned no registered intervention study at the evidence freeze.
Evidence Strength and Unresolved Questions
| Question | Established | Unresolved |
|---|---|---|
| Chemical identity | GVSWGLR, formula, mass, CAS, PubChem record, and sortilin-propeptide lineage. | Salt form of the current Apex material and comparability across manufactured lots. |
| Direct target assay | Inhibition in an engineered hTREK-1/HEK line and biphasic action in a separate paper. | Universal channel mechanism, tissue dependence, and exact concentration-response across systems. |
| In vivo evidence | Originating-group mouse behavioral, stroke, neurogenesis, and synaptogenesis observations. | Independent exact-peptide replication, other species, exposure-response, and translational relevance. |
| Human evidence | Endogenous parent-propeptide biomarker measurements. | Administered-peptide PK, safety, efficacy, and dose response. |
| Trial record | No registered PE-22-28 or spadin trial located in the frozen search. | Whether future genuine studies will establish a clinical evidence lane. |
The peripheral evidence is also a reminder that TREK-1 is not confined to one brain pathway. The spadin safety screen records as background that TREK-1 deletion increases sensitivity to pain, seizures, and ischemia (Moha Ou Maati et al. 2012). Spadin work reports pancreatic insulin effects (Hivelin et al. 2016), while sortilin-deficient mice show broader behavioral changes (Moreno et al. 2018). None establishes PE-22-28 safety.
What Analytical Documentation Can Verify
A defined seven-residue analyte permits an orthogonal identity plan: declared sequence and form, chromatographic behavior, and mass data that agree with the intended species. It still does not turn a product record into biological evidence. The HPLC guide explains method-dependent peak area, the mass-spectrometry guide explains ion-form attribution, and the COA guide shows how to match lot, method, date, and result.
- Sequence and form: documentation should identify GVSWGLR and state whether the material is the free peptide or a salt.
- HPLC: can report chromatographic purity under a stated detector and integration method; it does not establish identity, total content, sterility, endotoxin status, or activity.
- Mass spectrometry: an ion near the expected mass can support identity when the ion form and tolerance are explicit; mass alone cannot prove residue order.
- Lot traceability: product, batch, test date, methods, results, and released certificate should align in the Lab Verified archive.
- Handling boundary: where an approved laboratory protocol requires solution arithmetic, use the research reconstitution calculator; this guide supplies no procedure.
The current PE-22-28 product record is the separate destination for current commercial and lot facts; this guide does not treat product metadata as evidence for peptide lineage.
Frequently Asked Questions
What is PE-22-28?
PE-22-28 is a synthetic seven-residue peptide with the sequence Gly-Val-Ser-Trp-Gly-Leu-Arg, abbreviated GVSWGLR. It corresponds to positions 22–28 of the human sortilin propeptide and is also called mini-spadin in the originating literature. PubChem records CAS 1801959-12-5, formula C35H55N11O9, and average molecular weight 773.9 g/mol.
Is PE-22-28 the same as mini-spadin?
Yes. The originating research group uses mini-spadin for the seven-residue PE 22-28 sequence GVSWGLR. The alias matters because two primary papers use mini-spadin rather than the hyphenated product name. Modified analogs such as AVSWGLR are different molecules, and results attributed collectively to mini-spadin and its analogs should not be assigned to PE-22-28 alone.
Does PE-22-28 block TREK-1?
An engineered hTREK-1/HEK assay reported inhibition with an IC50 of 0.12 nM, but another study reported biphasic action: activation at lower tested doses and inhibition at higher tested doses. Independent parent-spadin experiments also disagree across systems. PE-22-28 is therefore more accurately described as a TREK-1 modulator under study than as a universally simple blocker.
Are there human studies or clinical trials for PE-22-28?
No administered-human study or registered clinical trial was located for PE-22-28 or spadin in the frozen evidence search. Human papers measured the endogenous sortilin-derived propeptide as a biomarker in depression or stroke cohorts. Those records do not establish PE-22-28 exposure, pharmacokinetics, safety, efficacy, or a human-use protocol.
What can analytical testing confirm for PE-22-28?
Lot-matched documentation can compare the declared GVSWGLR identity with chromatographic and mass-spectrometry results and connect those results to a batch and test date. HPLC peak area is method-dependent, while a matching mass does not prove sequence order, sterility, biological activity, safety, or efficacy. The salt form and ion assignment should be explicit.
Research Use Disclaimer
PE-22-28 is discussed as a research-grade chemical reagent for in-vitro and preclinical research only. It is not an approved pharmaceutical product, is not for human or veterinary consumption, and is not presented as a treatment. This page provides no dosing, administration, preparation, or medical guidance.
