Research Comparison

PE-22-28 vs Semax

PE-22-28 (Spadin-derived synthetic peptide (TREK-1 channel blocker)) and Semax (Synthetic ACTH(4-10) analog (heptapeptide)) are documented as co-studied in the PeptiDex library. This page puts the two entries side by side on class, molecular weight, half-life, origin, mechanism and studied research areas — every value taken from the entry it belongs to.

For research and educational purposes only. This page places two documented library entries next to each other. It is not medical advice, it does not rank one compound above the other or claim either is more effective, and it is not a usage, dosing, or combination recommendation.

Why these two are co-studied

Cross-referenced for research context — not a usage or combination recommendation.

From the PE-22-28 entryBoth are studied around BDNF and neurogenesis endpoints in mood/cognition research contexts.

At a glance

Side-by-side reference for PE-22-28 and Semax on compound class, research category, length, molecular weight, half-life and origin.
AttributePE-22-28Semax
Compound classSpadin-derived synthetic peptide (TREK-1 channel blocker)Synthetic ACTH(4-10) analog (heptapeptide)
Research categoryCognitive & NootropicCognitive & Nootropic
Length (amino acids)7 amino acids7 amino acids
Molecular weight773.9 g/mol813.9 g/mol
Half-lifeNot documented~2-5 minutes (plasma)
OriginPE-22-28 is a synthetic peptide derived from spadin, itself a fragment of the sortilin-derived propeptide (neurotensin receptor-3 propeptide), developed in academic pharmacology research primarily in France.Semax was developed in Russia (Institute of Molecular Genetics, Russian Academy of Sciences) as a synthetic analog of a fragment of adrenocorticotropic hormone (ACTH 4-10) with an added Pro-Gly-Pro tail for stability. It is marketed in Russia and some neighboring countries.

“Not documented” means the PeptiDex entry records no value for that field. Nothing on this page is estimated, and no figure is carried over from one compound to the other.

How PE-22-28 works

PE-22-28 is a shortened, modified analog of spadin designed to block the TREK-1 (two-pore-domain potassium) channel. Blockade of TREK-1 is associated in preclinical research with antidepressant-like effects and enhanced neurogenesis and synaptogenesis. It was engineered to improve stability relative to the parent spadin peptide.

How Semax works

Semax is an analog of the ACTH(4-10) melanocortin fragment but is described as being devoid of hormonal (corticotropic) activity. Research reports that it influences brain-derived neurotrophic factor (BDNF) and its receptor TrkB, modulates the expression of neurotrophin-related and immune genes, and may affect monoaminergic systems. It has been studied for neuroprotective and nootropic effects, potentially via effects on the melanocortin system.

Mechanistic descriptions reflect published research-literature understanding and are quoted from each compound's own entry. Much peptide research is preclinical (in-vitro or animal-model); mechanism in humans may differ and is not established for many compounds.

Where each one appears in the literature

The research contexts each entry documents. Listing a research area is not a claim of efficacy or a therapeutic indication, and the two lists are not scored against each other.

PE-22-28

Depression and antidepressant-like effects (preclinical)TREK-1 potassium channel modulationNeurogenesis and synaptogenesisNeuroprotection (preclinical)

Semax

Cognitive enhancement and memoryIschemic stroke recovery (studied in Russia)NeuroprotectionAttention and mental performanceBDNF/TrkB neurotrophic signaling

What sets each apart

PE-22-28

PE-22-28 is distinguished by its ion-channel (TREK-1) blocking mechanism aimed at antidepressant effects, unlike the neurotrophic or melanocortin peptides in this class.

Semax

Semax is a melanocortin (ACTH)-derived peptide oriented toward neuroprotection and cognition, whereas Selank derives from tuftsin and is oriented toward anxiolysis.

Frequently asked questions

What is PE-22-28?

PE-22-28, sometimes called mini-spadin, is a synthetic heptapeptide corresponding to residues 22-28 of the endogenous peptide spadin. It is studied in preclinical models of depression and neurogenesis as a proposed inhibitor of the TREK-1 potassium channel.

How does PE-22-28 relate to spadin?

Spadin is a fragment derived from the propeptide of the sorting receptor sortilin, and PE-22-28 is a shortened, optimized fragment of it. Research describes PE-22-28 as among the smallest spadin fragments that retains TREK-1 inhibitory activity, with improved stability over the parent peptide.

What is PE-22-28's proposed mechanism?

PE-22-28 is proposed to act as a TREK-1 channel blocker, a mechanism linked in preclinical work to antidepressant-like effects and increased hippocampal BDNF and neurogenesis. Rodent studies report antidepressant-like behavior emerging within days rather than the weeks typical of SSRIs.

What is Semax and what is it studied for?

Semax is a synthetic heptapeptide that adds a stabilizing Pro-Gly-Pro tail to the ACTH(4-7) fragment, developed at the Russian Academy of Sciences. It is studied in research models of cognition, attention, memory, and neuroprotection, where it is reported to upregulate BDNF and NGF messenger RNA in the hippocampus and cortex.

How does Semax achieve long effects despite a very short half-life?

The parent peptide has a plasma half-life of only about 2-5 minutes, yet its transcriptional effects on neurotrophic factors are measured over hours. The Pro-Gly-Pro tail slows peptidase cleavage relative to the native ACTH(4-7) fragment, allowing enough exposure to drive downstream BDNF/NGF signaling that outlasts the peptide itself.

Why is intranasal delivery emphasized in Semax research?

Intranasal administration provides direct nose-to-brain transport, achieving rapid CNS exposure without depending on blood-brain-barrier crossing from systemic circulation. Given the peptide's very short plasma half-life, this route is a common design choice in cognition and neuroprotection studies.

Answers are the ones published on each compound's own PeptiDex entry. They are educational summaries of research-literature context and are not medical advice.

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