PE 22-28
A seven-amino-acid peptide derived from spadin, a sortilin-derived peptide that blocks the TREK-1 potassium channel. It is studied in mouse models of depression for rapid-onset antidepressant-like effects.
Preclinical research
Size
1 option- Catalog no.
- PE10
- Specification
- 10ml*10vials
- Per kit
- 10 vials
For laboratory research use only. Not for human or animal consumption. Buyers must be 21 or older.
Overview
PE 22-28 was designed at the Institut de Pharmacologie Moléculaire et Cellulaire in France by shortening spadin, a 17-residue peptide (PE 12-28) cleaved from the propeptide released during maturation of sortilin, also called neurotensin receptor 3. Spadin was identified as an endogenous TREK-1 blocker with antidepressant-like activity in mice but has a short duration of action. PE 22-28 was derived from spadin's blood degradation products and showed higher TREK-1 affinity and longer-lasting effects in mouse studies. All published work is preclinical, and no human studies are indexed.
Class: Spadin-derived TREK-1 channel inhibitor peptide
Mechanism of action
How the compound acts, as described in the literature.
Inhibits TREK-1 (K2P2.1), a two-pore-domain potassium channel; in HEK cells expressing human TREK-1, PE 22-28 had an IC50 of 0.12 nM versus 40–60 nM for spadin (Djillani 2017).
TREK-1 deletion in mice produces a depression-resistant phenotype, and spadin's TREK-1 blockade increased firing of serotonergic neurons in the dorsal raphe nucleus (Mazella 2010).
In mice, PE 22-28 and its analogues reduced immobility in the forced swim test, induced neurogenesis after four days of treatment, and increased PSD-95 expression in cortical neurons.
Its reported duration of action in mice was up to 23 hours, compared with about 7 hours for spadin.
Published research
Selected studies, each linked to its PubMed record. Summaries describe what the studies reported.
2010
Mouse and in vitro study
PMID 20405001Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design.
Mazella J, et al. · PLoS Biol
Spadin bound TREK-1 with about 10 nM affinity, blocked channel activity in cells and hippocampal neurons, increased dorsal raphe serotonin neuron firing, and produced antidepressant-like effects in five behavioral tests in mice.
2017
In vitro and mouse study
PMID 28955242Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity.
Djillani A, et al. · Front Pharmacol
PE 22-28 inhibited human TREK-1 with an IC50 of 0.12 nM, reduced immobility in mouse depression tests, induced neurogenesis after four days, and acted for up to 23 hours versus 7 for spadin.
2019
Review
PMID 30291907Fighting against depression with TREK-1 blockers: Past and future. A focus on spadin.
Djillani A, et al. · Pharmacol Ther
Reviews TREK-1 as a depression target and strategies to optimize spadin, including retro-inverso, cyclized, and shortened analogues with greater TREK-1 inhibition and longer in vivo activity.
Evidence & safety
What the research does not show, and the adverse events and regulatory status it reports.
All data come from cell and mouse studies, largely from one French research group; no human pharmacokinetic, efficacy, or safety data exist. TREK-1 deletion in mice increases sensitivity to pain, seizures, and ischemia, so blocking the channel carries theoretical risks; spadin did not show these effects in mouse testing, but they have not been reported separately for PE 22-28.
Specifications
All sizes, exactly as catalogued.
| Catalog no. | Product | Specification | Vials per kit |
|---|---|---|---|
| PE10 | PE 22-28 | 10ml*10vials | 10 |
For laboratory research use only. Not for human or animal consumption. Not intended to diagnose, treat, cure or prevent any disease. Research summaries are provided for educational purposes and do not describe this product’s use.