PE-22-28

Overview

PE-22-28 is a 7-amino-acid synthetic analog of spadin, a peptide fragment (residues 22-28) of the 44-aa propeptide (PE) released during post-translational maturation of sortilin (the neurotensin receptor-3). It is studied in preclinical models as a fast-acting antidepressant that works by selectively blocking the TREK-1 two-pore potassium channel. There is no established use for hair growth — that is a separate compound and the two should not be confused.

Mechanism of Action

PE-22-28 is a highly selective antagonist of the TREK-1 (KCNK2) two-pore-domain potassium channel, with reported in vitro IC50 near 0.12 nM — roughly 300–500× more potent than the parent spadin peptide (IC50 ~40–60 nM). TREK-1 is enriched in serotonergic neurons of the dorsal raphe nucleus; blocking it depolarizes these neurons and enhances 5-HT transmission to limbic targets. In rodents, TREK-1 blockade also increases hippocampal neurogenesis and synaptic markers (PSD-95, BDNF), which is hypothesized to underlie its rapid-onset antidepressant signature.

Research Summary

Mazella, Borsotto and colleagues at Nice, France identified spadin (Mazella et al., PLoS Biology 2010, PMID 20405001) and subsequently developed shortened PE 22-28 analogs with ~300× improved TREK-1 affinity and longer in vivo half-life (Djillani et al., Front Pharmacol 2017, PMID 28955242). In mouse antidepressant assays (forced swim, tail suspension, novelty-suppressed feeding), acute or 4-day IP dosing at ~3–4 μg/kg produced effects comparable to chronic SSRI treatment; oral gavage at 1 mg/kg was also active. The G/A-PE 22-28 modification extended duration of action to ~21–23 hours. Chronic dosing did not produce cardiac or seizure signals in rodents. No human clinical trials have been conducted. A detailed review of TREK-1 blockers for depression is available in Djillani et al., Pharmacol Ther 2019 (PMID 30291907).

Vendors selling PE-22-28

Scored vendors carrying PE-22-28, ranked by trust grade. Grades are computed from indexed Certificates of Analysis. Full $/mg pricing is on the comparison page.

Prescribers who offer PE-22-28

3 prescribers in our directory work with PE-22-28, each confirmed from their own website. Peptides like PE-22-28 require a prescription from a licensed provider.

Reported Side Effects

• Unknown in humans — no clinical safety data
• Rodent studies did not report overt toxicity at effective doses
• Theoretical: potassium channel modulation could affect cardiac repolarization at higher exposures
• Injection site reactions (typical of SubQ peptides)

Compare PE-22-28 with Others

Research References

• Shortened spadin analogs display better TREK-1 inhibition, in vivo stability, and antidepressant activity (2017)
• Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design (2010)
• Fighting against depression with TREK-1 blockers: past and future. A focus on spadin (2019)

Frequently asked questions

Has PE-22-28 been independently lab-tested?

Disclosed Labs has collected 13 Certificates of Analysis (COA) for PE-22-28 from 7 independent testing labs. 10 vendors have submitted material for testing. Products average 99.6% tested purity across the corpus. Full testing data is available at https://www.disclosedlabs.com/peptides/pe-22-28/testing.

What is the average purity of PE-22-28 on the market?

Based on 13 COAs analyzed by Disclosed Labs, PE-22-28 products average 99.6% (±0.3%) tested purity. Individual vendor results vary; see per-vendor COA data at https://www.disclosedlabs.com/peptides/pe-22-28/coas.

Which labs have tested PE-22-28?

Independent labs that have tested PE-22-28 include: ILS Labs (Grade A). Full lab credibility grades and profiles are at https://www.disclosedlabs.com/labs.

Where can researchers source PE-22-28?

4 vendors with Disclosed Labs trust grades currently list PE-22-28, including Ion Peptide, Peptidology, Real Peptides. Compare live prices and lab-verified COAs at https://www.disclosedlabs.com/prices/pe-22-28.

Which prescribers offer PE-22-28 with a prescription?

3 prescribers in the Disclosed Labs directory work with PE-22-28, each confirmed from their own website. PE-22-28 requires a prescription from a licensed provider. Browse them at https://www.disclosedlabs.com/prescribers?peptide=PE-22-28.

How does PE-22-28 work?

PE-22-28 is a highly selective antagonist of the TREK-1 (KCNK2) two-pore-domain potassium channel, with reported in vitro IC50 near 0.12 nM — roughly 300–500× more potent than the parent spadin peptide (IC50 ~40–60 nM). TREK-1 is enriched in serotonergic neurons of the dorsal raphe nucleus; blocking it depolarizes these neurons and enhances 5-HT transmission to limbic targets. In rodents, TREK-1 blockade also increases hippocampal neurogenesis and synaptic markers (PSD-95, BDNF), which is hypothesized to underlie its rapid-onset antidepressant signature.

What does the research say about PE-22-28?

Mazella, Borsotto and colleagues at Nice, France identified spadin (Mazella et al., PLoS Biology 2010, PMID 20405001) and subsequently developed shortened PE 22-28 analogs with ~300× improved TREK-1 affinity and longer in vivo half-life (Djillani et al., Front Pharmacol 2017, PMID 28955242). In mouse antidepressant assays (forced swim, tail suspension, novelty-suppressed feeding), acute or 4-day IP dosing at ~3–4 μg/kg produced effects comparable to chronic SSRI treatment; oral gavage at 1 mg/kg was also active. The G/A-PE 22-28 modification extended duration of action to ~21–23 hours. Chronic dosing did not produce cardiac or seizure signals in rodents. No human clinical trials have been conducted. A detailed review of TREK-1 blockers for depression is available in Djillani et al., Pharmacol Ther 2019 (PMID 30291907).