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Seven residues of ACTH with a Pro-Gly-Pro tail: a Russian-origin neuropeptide with a large rodent literature and almost no Western trial data.
Also known as: Pro-Gly-Pro-ACTH(4-7) · Met-Glu-His-Phe-Pro-Gly-Pro · MEHFPGP
Part of the Neuropeptides & signaling cluster
Overview
Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) built from residues 4–7 of adrenocorticotropic hormone plus a C-terminal Pro-Gly-Pro tripeptide, developed in Russia as a neuroprotective and nootropic agent. It has a substantial rodent literature on ischaemic stroke and spinal cord injury and is registered as a medicine in Russia, but it is not approved in the US, Canada or the EU and has no registered trials on ClinicalTrials.gov.
Source & context
Biological / chemical source: Synthetic heptapeptide
Primary research or clinical context: Registered as a medicine in Russia; not approved in the US, Canada or the EU — sold elsewhere only as an unlicensed research chemical
What Semax is
Semax is a synthetic seven-residue peptide, Met-Glu-His-Phe-Pro-Gly-Pro, designed at the Institute of Molecular Genetics in Moscow. The first four residues are positions 4 to 7 of adrenocorticotropic hormone (ACTH), the fragment associated with the hormone's behavioural rather than adrenal effects; the Pro-Gly-Pro tail was added to slow enzymatic breakdown. It has no melanocortin-receptor steroidogenic activity and is studied as a neuroprotective and cognition-modulating agent. Almost the entire literature comes from Russian groups, and the compound is registered as a medicine in Russia for neurological indications. Outside Russia it has no marketing authorisation and is sold only as an unlicensed research chemical.
Sequence and chemistry
In one-letter code the sequence is MEHFPGP (molecular formula C37H51N9O10S, average mass about 814 Da). The N-terminal methionine and histidine of the ACTH core give the peptide a metal-binding site: Magrì et al. (Journal of Inorganic Biochemistry 2016) showed that Semax coordinates copper(II) and zinc(II) and that acetylating the N-terminus changes both the coordination mode and the biological readouts, which is one reason different preparations are not interchangeable. The peptide is small and linear, with no disulfide bridges or non-canonical residues; its stability advantage over native ACTH(4-10) comes entirely from the Pro-Gly-Pro extension.
Mechanism: what the animal studies point to
No single receptor has been established for Semax. A genome-wide expression study in rats with permanent middle cerebral artery occlusion (Medvedeva et al., BMC Genomics 2014) found that the peptide predominantly enhanced the expression of immune-system genes, which accounted for more than half of all Semax-responsive genes, and altered 24 vascular-system genes at 3 hours and 12 at 24 hours after occlusion. In a 2025 spinal cord injury study in female mice (Liu et al., British Journal of Pharmacology), Semax improved functional recovery, reduced lysosomal-membrane-permeabilisation-related pyroptosis, and was linked through RNA sequencing to the deubiquitinase USP18 and the μ-opioid receptor gene Oprm1. These are mechanistic leads, not a settled pathway.
Human data
Western-style randomised trials are absent. The most rigorous human study in the evidence pack is a resting-state functional MRI experiment in 52 healthy volunteers (Panikratova et al., Doklady Biological Sciences 2020) that compared Semax, Selank and placebo before and 5 and 20 minutes after administration; it reported changes in functional connectivity between the right amygdala and the right temporal cortex. Russian clinical use in ischaemic stroke is described in the literature, but the abstracts available do not report controlled outcome data. As of September 2026 there is no registered trial on ClinicalTrials.gov.
Pharmacokinetics
Published pharmacokinetic data for Semax are sparse in the English-language literature. The peptide is used intranasally in Russian practice, a route chosen because linear peptides of this size are degraded in the gut and cleared quickly from plasma; the Pro-Gly-Pro tail extends but does not eliminate that instability. No human half-life value appears in the evidence pack, and none is stated here.
Semax vs Selank
Semax and Selank are siblings from the same Moscow programme and are usually discussed together. Both are short synthetic peptides built on an endogenous fragment with a Pro-Gly-Pro tail — Semax on ACTH(4-7), Selank on the immunomodulatory tuftsin sequence — and both are registered in Russia. Semax is positioned as nootropic and neuroprotective, Selank as anxiolytic. The 2020 volunteer fMRI study tested them side by side and found both shared and distinct connectivity effects; beyond that, head-to-head evidence is thin. The Selank profile covers its own literature.
| Semax | Selank | |
|---|---|---|
| Parent fragment | ACTH(4-7) | Tuftsin (Thr-Lys-Pro-Arg) |
| Tail | Pro-Gly-Pro | Pro-Gly-Pro |
| Length | 7 aa | 7 aa |
| Positioning | Nootropic / neuroprotective | Anxiolytic |
| Status (Sept 2026) | Registered in Russia only | Registered in Russia only |
Regulatory status and the grey market
Semax is not approved by the FDA, Health Canada or the EMA and has never been submitted to them. It is sold online as a nasal spray or lyophilised powder under a “research” label, which does not make it lawful to market for human use in those jurisdictions. Because the N-acetylated and non-acetylated forms behave differently in metal-binding assays, and because vendor material is not batch-verified, a product labelled Semax cannot be assumed to match the peptide studied in the literature. This profile is educational and is not guidance on obtaining or using anything.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Met-Glu-His-Phe-Pro-Gly-Pro: residues 4–7 of ACTH (Met-Glu-His-Phe) extended with a Pro-Gly-Pro tripeptide that protects the fragment from rapid degradation
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- PubChem molecular record · 2026-10-01
- Molecular formula
- C37H51N9O10S
- Average reference mass
- ≈ 813.9
- Receptors
- No single receptor established. Proposed actions include modulation of BDNF/TrkB signalling and, in a 2025 mouse study, the μ-opioid receptor gene Oprm1; the ACTH core also binds copper(II) and zinc(II)
- Backbone
- Met-Glu-His-Phe-Pro-Gly-Pro: residues 4–7 of ACTH (Met-Glu-His-Phe) extended with a Pro-Gly-Pro tripeptide that protects the fragment from rapid degradation
- Status
- Registered medicine in Russia; not approved in the US, Canada or EU as of September 2026
The C-terminal Pro-Gly-Pro extension is the engineering step: it stabilises the ACTH(4-7) fragment against peptidases. An N-acetylated variant has been studied for its altered metal-ion coordination.
- PubChem CID: 9811102
- CAS RN: 80714-61-0
- UNII: I5FAL2585H
Chemistry values: curated profile, PubChem · fetched 2026-10-01.
Semax — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Met-Glu-His-Phe-Pro-Gly-Pro: residues 4–7 of ACTH (Met-Glu-His-Phe) extended with a Pro-Gly-Pro tripeptide that protects the fragment from rapid degradationAverage reference mass: 813.9 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Semax
What is Semax?+
Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) built from residues 4–7 of adrenocorticotropic hormone plus a C-terminal Pro-Gly-Pro tripeptide, developed in Russia as a neuroprotective and nootropic agent. It has a substantial rodent literature on ischaemic stroke and spinal cord injury and is registered as a medicine in Russia, but it is not approved in the US, Canada or the EU and has no registered trials on ClinicalTrials.gov.
What Canadian product status is recorded for Semax?+
Canadian product status for Semax has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Semax?+
Semax is commonly described as approximately 7 amino acids (Synthetic ACTH-fragment heptapeptide).
What is Semax?+
A synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) made from ACTH residues 4–7 plus a Pro-Gly-Pro tail, developed in Russia as a neuroprotective and nootropic agent.
Is Semax approved?+
It is registered as a medicine in Russia. It is not approved in the US, Canada or the EU, and no trial is registered on ClinicalTrials.gov as of September 2026.
How does Semax work?+
No single receptor is established. Rodent studies point to immune and vascular gene-expression changes after ischaemia and, in a 2025 mouse study, to USP18 and the μ-opioid receptor gene Oprm1.
Is there human evidence for Semax?+
Very little in the English-language literature: a 52-person healthy-volunteer fMRI study and descriptions of Russian clinical use. No Western randomised trial has been published.
What is the difference between Semax and Selank?+
Both are Russian Pro-Gly-Pro-tailed heptapeptides; Semax is built on ACTH(4-7) and positioned as nootropic, Selank on tuftsin and positioned as anxiolytic.
What is the sequence of Semax?+
MEHFPGP — Met-Glu-His-Phe-Pro-Gly-Pro. Formula C37H51N9O10S, average mass about 814 Da.
Further reading
- FoundationsWhat Are Research Peptides? A Clear Educational GuideLearn what “research peptides” means, how they differ from approved peptide drugs, quality markers (COA, purity), and how to study them responsibly.
- SafetyPeptide Safety and Risks: A Balanced Educational OverviewAn objective, balanced overview of what research does and does not establish about peptide risks—unknowns, purity and contamination concerns, and why unapproved compounds carry uncertainty. Not reassurance and not medical advice.
- CanadaAre Peptides Legal in Canada? A Regulatory GuideAn educational overview of how Health Canada regulates peptides—drug authorization, DINs, the “research use only” gray area, and import ambiguity. Not legal advice.
Related peptides
References & further reading
- 1.Panikratova et al. (2020). Functional Connectomic Approach to Studying Selank and Semax Effects. Dokl Biol Sci
- 2.Liu et al. (2025). Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice. Br J Pharmacol
- 3.Radchenko et al. (2025). The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer's Disease. Acta Naturae
- 4.Medvedeva et al. (2014). The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. BMC Genomics
- 5.Gusev et al. (2018). [The efficacy of semax in the tretament of patients at different stages of ischemic stroke]. Zh Nevrol Psikhiatr Im S S Korsakova
- 6.Magrì et al. (2016). Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties. J Inorg Biochem
- 7.Dolotov et al. (2006). Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. J Neurochem
- 8.Eremin et al. (2005). Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochem Res
- 9.Filippenkov et al. (2024). ACTH-like Peptides Compensate Rat Brain Gene Expression Profile Disrupted by Ischemia a Day After Experimental Stroke. Biomedicines
- 10.PubChem — Semax (CID 9811102)