pe-22-28

a seven amino acid peptide researched as an antidepressant, so far only in mice and in cells. three papers, one lab, zero humans, and the 23 hour duration printed on vendor pages was measured on a different molecule.

tier C · focus · 3 papers · zero humans

verdict

a seven amino acid peptide researched as an antidepressant. it blocks a potassium channel called TREK-1, and blocking that channel makes mice behave the way antidepressant drugs make them behave. the cell work runs a proper dose-response curve and the mouse results repeat, but every original paper comes from one CNRS lab, no human has ever received it, and how long it lasts in the body is unpublished.

on whether PE 22-28 does anything in people: nobody knows, because nobody has ever been given it. a july 2026 sweep of ClinicalTrials.gov returned zero studies for spadin, zero for PE 22-28 and zero for mini-spadin, and a PubMed search limited to clinical-trial publication types returned nothing either. the three human papers vendors point at drew blood and measured a protein the body already makes, the sortilin propeptide. the entire human record is a blood test.

on the 23 hour duration on the label: that number was measured on a different molecule. the origin paper timed how long the behavioural effect lasted and got four answers, 14, 17, 21 and 23 hours, all of them on the alanine-substituted analog G/A-PE 22-28 or on its biotinylated version. plain PE 22-28 sat out the duration experiment. the paper gives no serum half-life for it anywhere, and no pharmacokinetic study of the molecule has been published since.

on whether the TREK-1 mechanism holds up: the channel is a credible target and the peptide is the weaker half of the story. independent groups in nanjing, dalian, budapest and seoul have all published on TREK-1 blockade, and a 2025 mouse paper identified the channel as a target of the ketamine metabolite hydroxynorketamine. how this peptide blocks it is the contested part. a group at portsmouth put 1 micromolar spadin on arachidonic-acid-activated TREK-1 in xenopus oocytes, the frog egg cells used as a standard test bed, and saw no inhibition, on the mouse clone and on the human clone, at a concentration their own paper says should give about 75 percent block.

based on published preclinical evidence. research framing only. not medical advice.

why C-tier

C-tier, with the ceiling fixed before the argument starts. No human has ever received this peptide, so B is out of reach however clean the mouse work reads. It clears D because the preclinical work is genuine. The target is defined, the sequence is confirmed twice over by the propeptide recited in a granted patent and by that patent's own sequence listing, the electrophysiology runs a full dose-response curve, and the behavioural readouts repeat across four paradigms at 3 to 4 mcg/kg with large effect sizes. The published record also carries a real internal negative control, PE 22-27, the fragment that failed to block the channel, which is also reported ineffective in forced swim. Holding it at the bottom of C: every paper naming this exact molecule comes from one CNRS group, group sizes run five to ten animals, pharmacokinetics, toxicology and in vivo dose ranging on the plain peptide are all unpublished, one independent laboratory could not reproduce channel block on the parent peptide, the granted patents deliberately claim other molecules, and the reported direction of effect on TREK-1 reverses across a hundred-fold dose range with no mechanistic account. That is a low C. If a second laboratory publishes original data on this peptide, or a first-in-human study registers, the tier moves.

the core tension

the molecule is real and the target is credible, and almost every number sold with it was measured on something else. the 23 hour duration was measured on the biotinylated alanine analog at 40 mcg/kg. the granted US patent claims AVSWGLR and leaves the GVSWGLR being sold pointedly unclaimed, and the specification says why, everything except the alanine analog is a natural product. the potency multiplier is 333-fold in the patent, more than 300-fold in the origin paper, 40 to 350-fold in the lab's own review, and 300 to 500 on vendor pages. the one independent group that tried to reproduce channel block on the parent peptide came up empty. and the reported direction of effect on TREK-1 flips between 0.03 and 3 mcg/kg with no mechanistic account of why.

what it is

PE 22-28 is a piece of a human protein, seven amino acids long. Sortilin is built with a 44-amino-acid cap on the front, and the cell snips that cap off as the protein matures. PE 22-28 is a short stretch of the discarded cap. The granted CNRS patent writes the cap out as QDRLDAPPPPAAPLPRWSGPIGVSWGLRAAAAGGAFPRGGRWRR, and positions 22 to 28 of it read Gly-Val-Ser-Trp-Gly-Leu-Arg. The parent molecule is spadin, a longer stretch of the same cap, positions 12 to 28, described by the same lab in PLoS Biology in 2010. PE 22-28 is the shortened version. In print the lab calls it mini-spadin.

what it does

It blocks a potassium channel called TREK-1, and in mice that reads as an antidepressant. In a cell line built to carry the human channel, PE 22-28 blocked 55 percent of the arachidonic-acid-activated current at 100 nanomolar, across 13 recordings, at a reported IC50 of 0.10 to 0.12 nanomolar. TREK-1 is a two-pore potassium channel, and blocking it produces antidepressant-like behaviour in rodents in work from several independent groups. In mice, a single 3.0 mcg/kg intraperitoneal dose cut forced-swim immobility from 161.7 seconds to 91.8 seconds, ten animals per arm. Hippocampal BrdU-positive cell counts came in at 1736 against 899 for saline, five animals per arm.

origin

Institut de Pharmacologie Moleculaire et Cellulaire, CNRS, at Valbonne near Nice. Jean Mazella, Marc Borsotto and Catherine Heurteaux described spadin in PLoS Biology in 2010 and the shortened analogs in Frontiers in Pharmacology in 2017. An exact-string PubMed search turns up three records naming this molecule, the 2017 origin paper, a 2019 stroke paper and a 2021 beta-cell paper. All three come from that group. Outside reviews mention it and none of them generate data on it.

why researchers are interested

The pitch is potency and duration. Vendor pages describe a compound 300 to 500 times stronger than spadin that lasts about 23 hours, sold into the mood and nootropic corner of the market. Both numbers trace back to the same 2017 paper. Both were measured on modified versions, and the plain peptide sold under the name sat out both experiments.

does it work

In mice the behavioural readouts repeat across three papers and the effect sizes are large. In humans the question has never been asked. Group sizes run five to ten. The plain peptide was only ever given at 3.0 to 4.0 mcg/kg by injection and once by gavage at 1 mg/kg, and pharmacokinetics, toxicology and in vivo dose ranging all remain unpublished. The direction of effect on the target also reverses across a hundred-fold dose range, which the papers report and leave unexplained.

key facts

• molecular formula: C35H55N11O9
• molecular weight: 773.9 g/mol (calculated from the sequence; the patent arithmetic in this review used about 774)
• amino acids: 7
• half-life: not published. no pharmacokinetic study of PE 22-28 exists, and the origin paper reports no serum half-life number for it. the 23 h figure quoted by vendors is a behavioural half-effect time measured on the biotinylated alanine analog at 40 mcg/kg
• type: heptapeptide; fragment 22-28 of the sortilin (NTSR3) propeptide; TREK-1 blocker
• CAS: 1801959-12-5 circulates in vendor and catalogue listings; not confirmed against a primary registry in this review, and PubMed does not resolve it
• 3 papers naming this exact molecule
• 0 humans given PE 22-28 or spadin
• 5 mice per group in the neurogenesis result
• 1 laboratory behind every original paper

frequently asked questions

What is PE 22-28?

PE 22-28 is a seven-amino-acid piece of a human protein, researched as an antidepressant. It has been tested in mice and in cells, and never in a person, so everything known about it is preclinical. The sequence is Gly-Val-Ser-Trp-Gly-Leu-Arg, which is positions 22 to 28 of the cap that human sortilin sheds as it matures. It is a shortened version of spadin, and the originating laboratory calls it mini-spadin. Vendors label it PE 22-28 or PE-22-28. It is sold as a research chemical and has no approved human use anywhere.

What does PE 22-28 do?

In mice it reads as an antidepressant. A single injection was enough to move the forced-swim result, four behavioural tests moved the same way, and four days of dosing roughly doubled the count of newborn cells in the hippocampus. No person has ever received it, so none of that has been measured in a human. In a cell line built to carry the human TREK-1 channel it blocks that channel, inhibiting 55 percent of the arachidonic-acid-activated current at 100 nanomolar, at a reported IC50 of 0.10 to 0.12 nanomolar. In mice, 3.0 mcg/kg intraperitoneal reduced immobility in forced swim, reduced latency in novelty-suppressed feeding, shortened escape latencies in learned helplessness, and roughly doubled hippocampal BrdU-positive cell counts. A 2019 paper reports improved motor and cognitive deficits in a mouse stroke model. Every one of these results is preclinical and all of them come from one research group. Vendors also sell it as a nootropic, and no learning, memory or attention task in a healthy animal has been published on it.

How is PE 22-28 administered in the published research?

In the literature it was given to mice by intraperitoneal injection at 3.0 to 4.0 mcg/kg, with activity also reported from 0.03 mcg/kg in a stroke model, and the shortened analogs stayed active when given by gavage at 1 mg/kg. There is no human protocol, because there has been no human study. A july 2026 registry sweep returned zero studies for PE 22-28, mini-spadin or spadin.

Does PE 22-28 last 23 hours?

Not on the published record. The 23 hour figure is how long the behavioural effect lasted in mice given the biotinylated alanine analog at 40 mcg/kg. All four values the origin paper reports, 14, 17, 21 and 23 hours, were measured on G/A-PE 22-28 or its biotinylated form. Plain PE 22-28 was never included in that experiment, the paper reports no serum half-life number for it, and no pharmacokinetic study of it has been published.

What are the side effects of PE 22-28?

Nobody has characterised them. Toxicology, pharmacokinetics and human exposure are all missing for this peptide. The often-quoted line about being free of side effects is conditional in the original text, applies to spadin analogs generally, and rests on a battery of negative findings in mice, which is a much smaller thing than a toxicology package. The same laboratory's own record on glucose does not agree with itself: a 2011 paper reports glycaemia unchanged by spadin, and a 2016 paper reports that spadin at 8 mcg/kg intravenous roughly doubled plasma insulin in mice and cut the glucose area under the curve by 28 percent, under a section heading naming hypoglycaemia.

Is PE 22-28 FDA approved?

No. It has no FDA approval, no IND located on the public record, no EMA record and no registered clinical trial in any registry searched. It is sold as a research chemical. The two registry numbers that circulate alongside it, NCT01330160 and NCT06943365, are both observational and neither administers any compound.

related peptides

• dihexa: the other single-lab rodent neuro compound whose marketing numbers come from a related molecule
• humanin: same shape of human file: observational biomarker measurement, zero interventional trials
• semax: nootropic peptide with an actual human trial base, for the contrast
• selank: anxiolytic research peptide with a clinical record, thin but real

reptides grades the research record and cites the literature behind every call. research reference only; not medical advice.