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For research use only. Not for human or veterinary use. Not a drug, food, or dietary supplement.
AMIRAVOResearch Library

PE-22-28 vs Selank

PE-22-28 and Selank are both short peptides discussed for mood and anxiety, but they were designed around different targets and have reached very different stages of development 2,6. PE-22-28 is a 7-amino-acid fragment of spadin, a peptide derived from the sortilin propeptide, designed by a French CNRS group to block the TREK-1 potassium channel and studied only in cells and mice 1,2. Selank is a synthetic analogue of tuftsin, developed in Russia and listed in a 2022 review as an anxiolytic drug registered in the Russian Federation 6,9. Neither is FDA-approved 10,11.

Unbranded reference vial illustrating PE-22-28; not an actual product
PE-22-28
Not approved — research use only
Unbranded reference vial illustrating Selank; not an actual product
Selank
Approved outside the US

Side by side

FieldPE-22-28Selank
ClassSynthetic 7-amino-acid peptide; shortened analogue of spadin 2Synthetic heptapeptide (Thr-Lys-Pro-Arg-Pro-Gly-Pro) 5
Origin and structureDesigned from blood degradation products of spadin, itself derived from the propeptide of the neurotensin receptor 3/sortilin 1,2Tuftsin (a Thr-Lys-Pro-Arg fragment of the immunoglobulin G heavy chain) extended with Pro-Gly-Pro 6
Proposed mechanismBlocks TREK-1 potassium channels; in human TREK-1 cell assays it inhibited the channel at sub-nanomolar concentrations 2In rat brain membranes, acted as a positive allosteric modulator of GABA binding 5; altered expression of GABA-related genes in rat cortex 6
Half-lifeNo serum half-life value reported; in mice, the antidepressant-like effect of analogues lasted up to about 23 hours versus 7 hours for spadin 2Not located in the sources reviewed
Highest human trial phaseNo human studies; none found on ClinicalTrials.gov 13Russian clinical studies without a stated phase 7,8; no registered studies found on ClinicalTrials.gov 14
FDA statusNot FDA-approved; not in any 503A nomination category as updated 14 May 2026 11Not FDA-approved; listed among withdrawn category 2 compounding nominations with immunogenicity and impurity concerns (page current 22 April 2026) 10
Published human outcomesNone located in the sources reviewedIn 62 patients with generalised anxiety disorder or neurasthenia, anxiety-scale changes were reported as similar to medazepam 7
Safety signalsNo human safety data located in the sources reviewedFDA states it lacks important information on safety issues in humans 10
WADA statusNot named on the 2026 Prohibited List; S0 covers substances with no governmental approval for human use 12Not named on the 2026 Prohibited List 12
Who funded the evidenceFrench public funding (CNRS, Agence Nationale de la Recherche, Fondation de l'Avenir) 2Russian academic institutes; one gene-expression study funded by the Russian Science Foundation 6,9

PE-22-28: what the data says

PE-22-28 comes from a line of work on spadin, a 17-amino-acid peptide that in mice (animal data) bound and blocked the TREK-1 channel and produced antidepressant-like behaviour in five tests 1,3. To improve stability, the same group designed the 7-amino-acid fragment PE-22-28 2.

In human TREK-1 cell assays (cell data), PE-22-28 showed higher affinity for the channel than spadin 2. In mice (animal data), it and its analogues reduced immobility in the forced swim test, increased markers of neurogenesis and synaptogenesis, and showed longer action duration than spadin 2. A related shortened analogue, mini-spadin, was tested in a mouse stroke model with post-stroke depression-like behaviour 4. No human studies were identified 13.

Selank: what the data says

Selank was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences with the Zakusov Research Institute of Pharmacology 6. In rat brain membranes (animal tissue), it acted as a positive allosteric modulator of GABA binding 5, and in rats it changed the expression of genes involved in GABA neurotransmission 6.

Human data are limited to small Russian studies. In 62 patients with generalised anxiety disorder or neurasthenia, 30 received Selank and the comparison group received medazepam; authors reported similar anxiety-scale changes in both groups 7. A separate study in patients with anxiety-asthenic disorders reported changes in serum cytokine balance 8. A 2022 review lists Selank among peptide drugs registered in Russia, classed as an anxiolytic 9.

Key research differences

  • Target: PE-22-28 was designed to block TREK-1 potassium channels 2, while Selank work points to allosteric modulation of GABA receptors 5.
  • Parent molecule: PE-22-28 is a fragment of the sortilin-derived peptide spadin 2, whereas Selank is an extended analogue of the immunoglobulin-derived peptide tuftsin 6.
  • Human data: no human studies of PE-22-28 were identified 13, while Selank has small Russian clinical studies 7,8.
  • Registration: Selank is listed as registered in Russia 9; PE-22-28 has no approval in the sources reviewed 11.
  • FDA compounding: Selank appears among withdrawn category 2 nominations 10, while PE-22-28 does not appear in any 503A category 11.

Where the evidence is limited

There is no direct comparison of PE-22-28 and Selank in any model. PE-22-28 has been studied only in cells and mice, mostly by the group that designed it 2,3. Selank's human studies are small, published in Russian and mostly from the developer's network, without independent replication in the sources reviewed 7,8. Behavioural tests in mice are not validated predictors of outcomes in people.

Frequently asked questions

Are PE-22-28 and Selank related?
No. PE-22-28 is a fragment of spadin designed to block TREK-1 channels 2, while Selank is a tuftsin analogue studied for GABA receptor modulation 5,6.
Has PE-22-28 been tested in humans?
No human studies were identified. Its evidence comes from human-channel cell assays and mouse behavioural models 2,13.
Can PE-22-28 and Selank be compared directly?
Not on current evidence. No study has tested them side by side, and only Selank has human data, from small Russian studies 7,13.
What does the FDA say about Selank?
The FDA lists selank acetate among withdrawn category 2 compounding nominations, citing immunogenicity and impurity risks and a lack of human safety information 10.

References

  1. Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design PLoS Biology. 2010
  2. Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity Frontiers in Pharmacology. 2017
  3. Fighting against depression with TREK-1 blockers: Past and future. A focus on spadin Pharmacology & Therapeutics. 2019
  4. First evidence of protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptides Neuropharmacology. 2019
  5. Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity Protein and Peptide Letters. 2018
  6. Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission Frontiers in Pharmacology. 2016
  7. Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia (in Russian) Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2008
  8. Immunomodulatory effects of selank in patients with anxiety-asthenic disorders (in Russian) Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2008
  9. Development of Peptide Biopharmaceuticals in Russia Pharmaceutics. 2022
  10. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 04/22/2026) FDA (Human Drug Compounding). 2026
  11. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (updated May 14, 2026) FDA. 2026
  12. Prohibited List (2026 List, in force 1 January 2026) World Anti-Doping Agency. 2026
  13. ClinicalTrials.gov registry search: PE-22-28 and spadin (no registered studies returned, searched 24 October 2026) ClinicalTrials.gov. 2026
  14. ClinicalTrials.gov registry search: selank as intervention (no selank studies returned, searched 24 October 2026) ClinicalTrials.gov. 2026

For research use only. Not for human or veterinary use. Not a drug, food, or dietary supplement. This page compares published research and is not medical advice or a recommendation.