How is this different from conventional antidepressants?

Mechanistically it sits outside the monoamine story entirely. That makes it interesting as a research tool and also means there is no clinical experience with the target to draw on: no approved drug acts at TREK-1.

Has PE-22-28 been tested in humans?

No. There is no human data of any kind — no trial, no pharmacokinetic study, no case series. The entire literature is rodent and cell work.

A peptide released during maturation of the sortilin propeptide. PE-22-28 is a shortened fragment of it, developed for better stability and better inhibition of the channel.

Is PE-22-28 approved anywhere?

No. It has never entered a published clinical trial and is supplied here as a laboratory reagent for in-vitro research only.

Research guides

PE-22-28 (spadin analogue): what the research says

A TREK-1 blocker that came out of mouse genetics rather than drug screening, putting it outside the monoamine story entirely. All of it is preclinical.

Available in the catalogue

Supplied as research material. Sizes and pricing are on the product page. Availability is not a statement about what a compound does.

PE-22-28
Nootropic & Cognitive

PE-22-28 is mechanistically the most interesting compound in this section, because the target it acts on came out of a mouse genetics result rather than from modifying an existing drug class.

What the molecule is

A seven-amino-acid fragment of spadin, itself a peptide released during maturation of the sortilin propeptide. The shortened analogues were developed specifically to improve on spadin's stability and potency at the target.

Why TREK-1 became a target at all

TREK-1 is a two-pore-domain potassium channel. Deleting it in mice produces a phenotype resistant to depression-like behaviour, and that genetic result — not a screening programme against known antidepressants — is what made the channel interesting. A blocker of TREK-1 is therefore mechanistically distinct from the monoamine-based antidepressant literature rather than a variation on it.

That distinctness is the reason the compound is worth a research reagent's attention and also the reason there is no clinical evidence: a target with no approved drugs against it has no clinical programme to draw on.

What the published work reports

The founding paper on the shortened analogues reported better TREK-1 inhibition, better in-vivo stability and antidepressant-like activity in rodent models compared with spadin itself. Later work characterised how spadin interacts with the channel, including that it selectively antagonises arachidonic acid activation of TREK-1, and a separate paper reported effects of sortilin-derived peptides in a stroke recovery model.

All of it is rodent and cell work. There is no human data of any kind.

What studies reported

Each entry states what a study examined and the model it used. Nothing below describes an outcome for a person.

Everything below is drawn from published research, and each entry names the model the study used. Approval status varies by compound and by country, and nothing described here is supplied as a medicine or for use in a person.

Djillani et al. (2017)Frontiers in Pharmacology · 8:643
Reported that shortened spadin analogues displayed better TREK-1 inhibition, greater in-vivo stability and antidepressant-like activity in rodent behavioural models than spadin itself.
mouse and in vitro Source
Mazella et al. (2018)Frontiers in Pharmacology · 9:1541
Reviewed the role of sortilin/NTSR3 as the progenitor of spadin and its involvement in the membrane expression of TREK-1.
review of in vitro and rodent work Source
Ma et al. (2020)Frontiers in Pharmacology · 11:434
Reported that spadin selectively antagonises arachidonic acid activation of TREK-1 channels, characterising the interaction in more detail.
in vitro, electrophysiology Source
Pietri et al. (2019)Neuropharmacology · 158:107715
Reported protective effects of sortilin-derived peptides on stroke recovery and on post-stroke depression-like behaviour.
rodent, stroke model Source

Adverse and null findings reported

No dedicated safety study has been published for this compound. That is not a finding that none exists — it means the question has not been asked in print, and the gaps below say so.

What the research does not establish

An absence cannot be cited, so these are stated plainly. They are the part of the picture that silence would otherwise hide.

The `adverse` list is empty because no toxicology or safety study of this peptide has been published, not because it has been examined and found benign. For a compound acting on an ion channel expressed in cardiac and neural tissue, that absence is worth stating explicitly.
There is no human data of any kind. No trial, no pharmacokinetic study, no case series.
TREK-1 is expressed outside the brain, including in cardiac tissue. What systemic blockade of it does has not been characterised in the published work on this peptide.
The antidepressant-like activity is measured in rodent behavioural models, which are screening tools rather than measurements of mood. Their track record at predicting human antidepressant efficacy is mixed.
No approved drug acts at TREK-1, so there is no clinical experience with the target class to borrow from.
It holds no marketing authorisation anywhere and has never entered a published clinical trial.

Common questions

What does PE-22-28 target?: TREK-1, a two-pore-domain potassium channel. It became a target because deleting it in mice produces a phenotype resistant to depression-like behaviour — a genetics result rather than a drug-screening one.
How is this different from conventional antidepressants?: Mechanistically it sits outside the monoamine story entirely. That makes it interesting as a research tool and also means there is no clinical experience with the target to draw on: no approved drug acts at TREK-1.
Has PE-22-28 been tested in humans?: No. There is no human data of any kind — no trial, no pharmacokinetic study, no case series. The entire literature is rodent and cell work.
What is spadin?: A peptide released during maturation of the sortilin propeptide. PE-22-28 is a shortened fragment of it, developed for better stability and better inhibition of the channel.
Is PE-22-28 approved anywhere?: No. It has never entered a published clinical trial and is supplied here as a laboratory reagent for in-vitro research only.

Compounds covered

The reference page for each compound this article discusses.

PE-22-28

Selank (TP-7): what the research says
A tuftsin-derived anxiolytic registered as a medicine in Russia. Its defining reported property is what it lacks: sedation. The rodent evidence, and the limits.
Semax: what the research says
An ACTH(4-10) analogue registered as a medicine in Russia and unknown to Western regulators. What the BDNF work reported, and why the English record looks thin.
How to store research peptides
Lyophilised peptides at -20°C, reconstituted at 2–8°C, ambient in transit. Why the dry cake tolerates shipping, and what actually degrades a vial.

About this article

Everything reported here comes from published research, and each finding names the model the study used — cell culture, rat, or human. Findings in one model do not transfer to another, most of the work described is preclinical, and none of it is a claim that a compound is safe or effective for any purpose. Nothing on this page describes doses, routes of administration, or use in a person.

Approval status varies by compound and by country. A few of the substances described are the active ingredient of medicines authorised in the EU; most have no marketing authorisation anywhere and have never been assessed by a regulator. Neither is supplied as a medicine here. All material supplied by ASSAY is sold for in-vitro laboratory research only, and is not a drug, food, cosmetic or medical device, and not for human or veterinary use.

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