PE-22-28

PE-22-28 is a seven-amino-acid spadin analog developed from degradation mapping of spadin, a sortilin-derived peptide that blocks TREK-1 potassium channels. The best direct evidence is preclinical: patch-clamp work in hTREK-1/HEK cells and rodent behavioral studies reported stronger TREK-1 inhibition and antidepressant-like activity compared with the parent peptide spadin. Earlier spadin work supports the broader mechanism by linking sortilin-derived peptide activity, TREK-1 inhibition, and antidepressant-like effects in mouse models. The evidence is direct, peer-reviewed, and mechanistically coherent, but it remains animal and cell-model evidence. PE-22-28 should be presented as a TREK-1/spadin-analog research compound, not as a human mood or cognitive treatment.

TREK-1 Channel Research

PE-22-28 was designed as a shortened spadin analog and showed potent TREK-1 channel inhibition in hTREK-1/HEK patch-clamp experiments ^[1].

Rodent Behavioral Models

In mouse behavioral models, PE-22-28 and related derivatives reduced immobility or escape-latency measures commonly used in antidepressant-like screening ^[1].

Parent Spadin Context

Parent spadin research supports the mechanistic link between sortilin-derived peptides, TREK-1 blockade, and antidepressant-like effects in rodents ^[2].

No Human Dataset

PE-22-28 evidence is preclinical; no defensible human safety, dosing, or efficacy conclusions can be made from the available literature ^[1].

Ion-Channel Translation Caveat

TREK-1 is a broadly relevant ion channel, so off-target physiology and chronic exposure questions remain unresolved without formal toxicology and clinical data ^[1][2].