Is PE-22-28 approved as a medicine, and where?

No. PE-22-28 is not approved for human use. The available evidence comes almost entirely from laboratory and animal studies.

What is PE-22-28 studied for?

PE-22-28 is most often discussed in the context of cognition, mood & sleep. Research has examined TREK-1 (K2P) potassium-channel pharmacology, Depression models in rodents, and Post-stroke neuroprotection in rodents. Being studied for an area does not mean it is proven or approved for it.

Does PE-22-28 have human clinical trials?

No. The evidence for PE-22-28 is almost entirely from cell and animal studies; there are no established human clinical trials.

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Nootropic & Neuropeptides

PE-22-28

PE 22-28; Mini-spadin; Spadin analog (PE 22-28)

5 min read · Updated October 9, 2026 · 12 references

Curated by PeptideInfo Wikilast reviewed October 9, 2026how we verify

Explored forCognition, mood & sleep

In brief · TL;DR

Preclinical — animal/in-vitro only

Spadin-derived heptapeptide (GVSWGLR) and TREK-1 inhibitor studied only in cells and mice, almost entirely by one CNRS group. Antidepressant-like effects are mouse-only. No human data, no trials, no approval, no verified CAS or PubChem CID. Vendor labels calling it a galanin or BDNF fragment are wrong.

Evidence: Evidence is largely animal/cell studies, not humans.

Sequence GVSWGLR (7 aa) = positions 22–28 of spadin (sortilin propeptide PE 12–28); designed from spadin's degradation products in blood
TREK-1 (K2P2.1 / KCNK2) inhibitor in vitro — reported IC50 0.12 nM vs 40–60 nM for spadin (one group; biphasic effect reported in 2019)
Antidepressant-like, neurogenesis and stroke-protection findings are mouse or cell data only
No human administration data, no ClinicalTrials.gov interventional study and no approval anywhere
Not a galanin fragment, not a BDNF fragment or TrkB agonist; spadin's PubChem CID/CAS do not apply to PE-22-28

↓ Read the full referenced entry below

PE-22-28 ("mini-spadin") is a synthetic seven-amino-acid peptide (GVSWGLR) corresponding to positions 22–28 of spadin, a fragment of the sortilin propeptide. It inhibits the TREK-1 potassium channel in cell and rodent studies from a single French research group. No human administration study, clinical trial or regulatory approval exists. It is not a galanin fragment and not a BDNF peptide.

Body & signals →

No receptor relationship mapped here yet. This does not mean the molecule has no biological effects.

Review pending

Contents7

Editorial review pending — noindex

This page remains under independent editorial review (reviewPending). It is visible in the wiki but noindexed. Educational reference only — not prescribing or self-use guidance.

Section 1 of 7Overview

Overview

PE-22-28 (also written PE 22-28, called "mini-spadin" in later papers) is a synthetic heptapeptide with the sequence GVSWGLR (Gly-Val-Ser-Trp-Gly-Leu-Arg). It corresponds to positions 22–28 of spadin, which is itself the 17-amino-acid fragment PE 12–28 of the 44-amino-acid sortilin propeptide (PE) released when NTSR3/sortilin is processed. Researchers designed it from spadin's degradation products in blood (Djillani et al. 2017).

Its reported target is TREK-1 (K2P2.1, gene KCNK2), a member of the two-pore-domain (K2P) potassium-channel family. Almost all published work comes from one research group (CNRS-IPMC, Valbonne/Sophia Antipolis, France — Mazella, Borsotto, Heurteaux and colleagues). No independent replication of PE 22-28 was found.

There are no human administration data. No ClinicalTrials.gov interventional study, no sponsor and no regulatory approval exist for PE-22-28 or spadin.

Not a galanin or BDNF fragment

Some vendor listings describe PE-22-28 as a galanin fragment / GalR2 agonist ("galanin 2-11"), as a BDNF-derived hexapeptide or TrkB agonist, as developed at a Russian academy, or give a different sequence. These descriptions are wrong: PE-22-28 is a 7-residue spadin (sortilin-propeptide) derivative with no sequence similarity to galanin(2-11) or BDNF, developed at CNRS, France. The BDNF link in the literature is a downstream marker measured after spadin in mice (Devader et al. 2015), not a direct mechanism of PE-22-28. Why vendors mixed these up is not documented; a catalogue conflation is only a hypothesis.

Section 2 of 7Identity

Identity

Property	Finding
Name	PE 22-28 / PE-22-28; "mini-spadin" (PMID 28955242; 31325429)
INN / USAN	None — no clinical programme
Sequence	GVSWGLR, 7 aa — positions 22–28 of spadin (PE 12–28: APLPRWSGPIGVSWGLR). Derived from spadin's sequence and the numbering in Djillani 2017, Table 1 (full text)
Parent peptide	Spadin (PE 12–28, 17 aa), from the sortilin propeptide (PE, 44 aa) (PMID 20405001)
PubChem CID	None found for "PE-22-28"
CAS	Not verified — no regulator or PubChem source; vendor CAS numbers are not reproduced
Not to be reused	Spadin's PubChem CID 91826106 / CAS 1270083-24-3 belong to spadin (the PubChem record carries an N-terminal Tyr), not to PE-22-28
Target	TREK-1 inhibitor (K2P2.1) — see below
Approval	None (FDA, EMA or elsewhere)

Section 3 of 7Mechanism (preclinical)

Mechanism (preclinical)

Spadin (the parent) binds TREK-1 with roughly 10 nM affinity and blocks the channel in mice and cell systems (Mazella et al. 2010, PLoS Biol).
PE 22-28 inhibited human TREK-1 expressed in HEK cells with a reported IC50 of 0.12 nM, versus 40–60 nM for spadin (patch clamp; Djillani et al. 2017).
In a 2019 mouse focal-ischaemia study, the same group reported a biphasic effect — TREK-1 activation at low concentration and inhibition at high concentration — which complicates describing it simply as an "inhibitor" (Pietri et al. 2019).

Section 4 of 7What the research shows

What the research shows

Human data

No study has given PE-22-28 or spadin to people. PubMed (spadin, "PE 22-28", "mini-spadin") and ClinicalTrials.gov searches (2026-10-09 dossier) found no phase 0/1 work and no interventional trial.
The only human material concerns the endogenous sortilin propeptide as a serum biomarker: levels rose after ECT in responders with treatment-resistant depression (n=45; Roulot et al. 2018), and serum propeptide was associated with depression scores after stroke in the STROKDEM cohort (n=204; Mazella E et al. 2025). No peptide was administered in either study; these findings are not evidence that PE-22-28 works.

Animal and cell data

Antidepressant-like behaviour in mice (forced-swim and novelty-suppressed-feeding tests), neurogenesis after 4 days, increased PSD-95 in cortical neurons, and an in vivo duration of action of up to 23 h versus 7 h for spadin (Djillani et al. 2017). The "4 days" refers to a mouse treatment window, not a clinical onset.
Stroke and post-stroke depression model in mice: protective effects reported for mini-spadin (Pietri et al. 2019).
Pancreatic beta cells in vitro: spadin and mini-spadin protected against IL-1β via CaMK/CREB, and mini-spadin promoted proliferation (Daziano et al. 2021).
The group's 2019 review summarises spadin optimisation (retro-inverso, cyclisation, shortening) and calls PE 22-28 a "promising molecule" (Djillani et al. 2019). No clinical programme has followed — so none has been discontinued.

Section 5 of 7Claims vs evidence

Claims vs evidence

Claim	Assessment
Spadin derivative (sortilin propeptide)	Supported (PMID 28955242)
Selective, potent TREK-1 inhibitor (IC50 ~0.12 nM)	Supported in vitro — one group; biphasic effect reported in 2019
Antidepressant effect	Weak — animal only (mouse FST/NSF); no human data
"Faster than SSRIs" / "works in 4 days"	Weak — animal only; mouse treatment window, not clinical
Neurogenesis / synaptogenesis	Weak — animal/in vitro only
Stroke neuroprotection	Weak — animal only (PMID 31325429)
Nootropic / cognitive enhancement in humans	Missing — no source
Galanin fragment / GalR2 agonist	False — GVSWGLR ≠ galanin(2-11)
BDNF fragment, BDNF mimetic or TrkB agonist	False — BDNF rise is a downstream marker after spadin (PMID 25598009)
Developed at a Russian academy	False — developed at CNRS, France
Safe in humans / "no side effects"	Missing — no human safety data; the "absence of TREK-1-related side effects" finding (PMID 21807005) concerns spadin in mice
Dosing / protocols	Not provided — no established regimen

Section 6 of 7Related pages

Semax, Selank — other peptides marketed as antidepressant/nootropic (different mechanisms)
Noopept, Dihexa — other preclinical-leaning "neurotrophic"/nootropic compounds

Section 7 of 7What this page intentionally omits

What this page intentionally omits

Any human dose, animal-dose conversion, reconstitution or protocol
Vendor CAS numbers and spadin's CID/CAS applied to PE-22-28
Galanin, BDNF or TrkB presented as PE-22-28's mechanism
"Fast-acting antidepressant" claims without the qualifier in mice

References12

References

1.
PE 22-28 primary paper — TREK-1 inhibition, mouse antidepressant-like effects and neurogenesis — Djillani A, et al., Frontiers in Pharmacology, 2017. source
2.
PE 22-28 primary paper — PMC full text (sequence numbering, Table 1) — PubMed Central, 2017. source
3.
Spadin (parent peptide) — TREK-1 binding/blockade and antidepressant-like phenotype in mice — Mazella J, et al., PLoS Biology, 2010. source
4.
Mini-spadin in focal ischemia and post-stroke depression (mouse) — Pietri M, et al., Neuropharmacology, 2019. source
5.
Spadin and mini-spadin protect beta cells against IL-1β (in vitro) — Daziano G, et al., Pharmacological Research, 2021. source
6.
Review of spadin optimisation (same research group) — Djillani A, et al., Pharmacology & Therapeutics, 2019. source
7.
Spadin increases hippocampal BDNF (spadin, not PE 22-28) — Devader C, et al., British Journal of Pharmacology, 2015. source
8.
Serum sortilin propeptide after ECT in treatment-resistant depression (endogenous biomarker; no peptide given) — Roulot M, et al., Neuropsychiatric Disease and Treatment, 2018. source
9.
Serum propeptide and post-stroke depression scores — STROKDEM cohort (endogenous biomarker; no peptide given) — Mazella E, et al., Journal of the Neurological Sciences, 2025. source
10.
Spadin safety findings in mice (absence of TREK-1-related side effects; spadin only) — PubMed. source
11.
PubChem CID 91826106 — spadin (parent peptide, NOT PE-22-28) — PubChem. source
12.
ClinicalTrials.gov search — spadin (no interventional studies with the peptide) — ClinicalTrials.gov. source

Frequently asked questions4

Frequently asked questions

What is PE-22-28?: PE-22-28 ("mini-spadin") is a synthetic seven-amino-acid peptide (GVSWGLR) corresponding to positions 22–28 of spadin, a fragment of the sortilin propeptide. It inhibits the TREK-1 potassium channel in cell and rodent studies from a single French research group. No human administration study, clinical trial or regulatory approval exists. It is not a galanin fragment and not a BDNF peptide.
Is PE-22-28 approved as a medicine, and where?: No. PE-22-28 is not approved for human use. The available evidence comes almost entirely from laboratory and animal studies.
What is PE-22-28 studied for?: PE-22-28 is most often discussed in the context of cognition, mood & sleep. Research has examined TREK-1 (K2P) potassium-channel pharmacology, Depression models in rodents, and Post-stroke neuroprotection in rodents. Being studied for an area does not mean it is proven or approved for it.
Does PE-22-28 have human clinical trials?: No. The evidence for PE-22-28 is almost entirely from cell and animal studies; there are no established human clinical trials.

Educational disclaimer. This article summarizes published research for informational purposes and is not medical advice. PE-22-28 is a research chemical not approved for human use. Consult a qualified healthcare professional before making health decisions.

References

Frequently asked questions

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