PE-22-28

Last Updated: August 2026

PE-22-28 is a synthetic seven-amino-acid peptide — residues 22–28 of spadin, a naturally occurring fragment cleaved from the sortilin propeptide that selectively blocks the TREK-1 potassium channel. PE-22-28 was engineered as a shorter, far more potent and more stable spadin analog, and is studied as a fast-acting antidepressant research tool. It is not approved and is supplied for research use only. Critically, all of its evidence comes from rodent studies — there are no human clinical trials.

What is PE-22-28 and how does the TREK-1 mechanism work?

TREK-1 is a two-pore-domain potassium channel that lets potassium leak out of neurons and quiets them; by selectively blocking TREK-1, PE-22-28 reduces that leak, making mood-relevant neurons easier to fire and — in animal models — restoring glutamatergic signaling and stimulating hippocampal neurogenesis and synaptogenesis, the proposed basis for a fast antidepressant-like effect. It is highly potent in vitro (TREK-1 IC₅₀ ≈ 0.12 nM, roughly 300–500× spadin)1 source specific to TREK-1 (sparing TREK-2, TRAAK, TRESK, and TASK-1).

What does the research on PE-22-28 show — and what are its limits?

The core data come from a 2017 Frontiers in Pharmacology paper (Djillani and colleagues) that screened shortened spadin analogs and found PE-22-28 produced strong TREK-1 inhibition, good in-vivo stability, and antidepressant-like behavior in mice, with increased hippocampal neurogenesis; the broader spadin/TREK-1 story traces to Mazella et al. (2010).1 source1 source But this must be stated plainly: all evidence is preclinical and in rodents, and whether TREK-1 blockade produces a genuine antidepressant effect in people is unproven. Evidence level: Rodent only.

What are the safety and regulatory considerations?

PE-22-28 is not approved for human use and has no human safety or efficacy data of any kind; it should be regarded strictly as a preclinical research compound. See the legal status guide. This is a research profile, not treatment guidance; anyone dealing with depression should speak with a qualified professional.

Why does vendor verification matter, and how does Peptigrity verify?

As a short synthetic peptide with essentially no clinical footprint, PE-22-28's identity and purity can only be established analytically — HPLC and mass-spec are the objective checks. Peptigrity collects independent third-party Certificates of Analysis for PE-22-28 from shops' official channels and verifies each for authenticity before publishing. Because shops choose which COAs to publish, results reflect the batches shops have made public rather than every production batch — a selection bias we state openly. A community-funded Testing Grant to purchase and test vials anonymously is in development. Tests in the database come from independent labs such as Janoshik Analytical, Freedom Diagnostics, and Chromate. See how to read lab results.

Educational information only; not medical advice. PE-22-28 is a preclinical research compound with no human data and is not approved. If you are dealing with depression, please consult a qualified healthcare professional. Peptigrity does not sell, endorse, or recommend products or vendors.