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Semax is a synthetic seven-amino-acid peptide (Met-Glu-His-Phe-Pro-Gly-Pro) made by joining a fragment of adrenocorticotropic hormone, ACTH(4-7), to a Pro-Gly-Pro tail. It was developed in Russia, where it is on the national list of vital and essential medicines1, but it is not an FDA-approved drug2, has no EU centralised authorisation3 and is not named in Australia's Poisons Standard4. Most of what is known about it comes from rat experiments and small Russian-language clinical studies.
This overview sets out what the published research on the Semax peptide reports, what it does not, and how much weight each kind of study can bear. It is written for people reading the scientific literature, not as guidance on use.
Semax is a heptapeptide: seven amino acids joined by peptide bonds. Its first four residues (Met-Glu-His-Phe) are positions 4 to 7 of ACTH, the pituitary hormone that stimulates the adrenal cortex. The last three (Pro-Gly-Pro) are a so-called glyproline tail, added to increase resistance to peptidases, the enzymes that cut peptides apart.1
You will see Semax described in two ways that mean the same molecule. Some papers call it an "analogue of ACTH(4-10)", because the natural fragment ACTH(4-10) reads Met-Glu-His-Phe-Arg-Trp-Gly and Semax replaces the last three residues. Others call it "ACTH(4-7)PGP", which describes how it is actually built. Despite that parentage, Semax is reported to have no hormonal activity: it does not act on the adrenal glands the way ACTH does.1 Research interest has always centred on the brain.
Chemical identifiers below are as listed by PubChem.5
| Property | Semax |
|---|---|
| Class | Synthetic heptapeptide; ACTH(4-7) analogue with a C-terminal Pro-Gly-Pro |
| Sequence (one-letter) | MEHFPGP |
| Sequence (three-letter) | Met-Glu-His-Phe-Pro-Gly-Pro |
| Molecular formula | C37H51N9O10S |
| Molar mass | 813.9 g/mol |
| CAS number | 80714-61-0 |
| PubChem CID | 9811102 |
| Origin | Developed in Russia; most studies come from Russian Academy of Sciences institutes in Moscow |
Semax's status differs sharply by jurisdiction, so it is worth being exact.
In short: Semax is a registered medicine in Russia. In the US, the EU and Australia it has no approval as a medicine, and the research-grade material sold for laboratory work is not a medicine anywhere.
The papers reviewed here do not identify a single receptor through which Semax acts. The mechanistic literature, almost entirely from rodents and cell culture, points mainly to two lines of evidence.
Brain-derived neurotrophic factor (BDNF) is a growth factor involved in synaptic plasticity. In a 2006 rat study, a single application of Semax (50 µg/kg) was reported to raise hippocampal BDNF protein about 1.4-fold and phosphorylation of its receptor, trkB, about 1.6-fold, with a threefold rise in one BDNF transcript. The treated rats also showed more conditioned avoidance responses in a learning task.7
A companion paper from the same group reported specific, reversible, calcium-dependent binding sites for tritium-labelled Semax in membranes from rat basal forebrain, and higher BDNF protein there three hours after intranasal application, but not in the cerebellum.8 That paper characterised binding sites, not a specific receptor protein.
Genome-wide studies in rats with an experimentally blocked middle cerebral artery report that Semax shifts the expression of many genes. A 2014 microarray study found that immune-response genes, particularly those for immunoglobulins and chemokines, made up more than half of the Semax-altered genes 24 hours after permanent occlusion, with further changes in vascular genes.9 A 2020 RNA-Seq study using temporary occlusion identified 394 differentially expressed genes at 24 hours compared with saline: inflammation-related genes were suppressed and neurotransmission-related genes activated.10
These are measurements of what changed in animal tissue. They do not demonstrate a mechanism, and they say nothing directly about people.
Experimental stroke (cerebral ischaemia) dominates the Semax literature, followed by learning, stress and a small amount of newer work in other injury models. The table summarises representative studies.
| Study | Model | What the authors reported |
|---|---|---|
| Dolotov et al., 20067 | Rats, single application | Higher hippocampal BDNF and trkB activation; more avoidance responses |
| Medvedeva et al., 20149 | Rats, permanent arterial occlusion | Altered immune and vascular gene expression |
| Filippenkov et al., 202010 | Rats, temporary arterial occlusion | 394 genes changed; inflammatory genes down, neurotransmission genes up |
| Inozemtseva et al., 202411 | Male rats, chronic unpredictable stress | Less stress-induced anhedonia and adrenal enlargement; hippocampal BDNF preserved; no effect in the forced-swim test |
| Liu et al., 202512 | Female mice, spinal cord contusion | Better locomotor recovery scores; μ-opioid receptor proposed as a target |
Most of the stroke studies use middle cerebral artery occlusion (MCAO) in rats: a filament or ligature blocks one of the main arteries supplying the brain, either permanently or for a set time before blood flow is restored. Permanent and temporary occlusion injure tissue in different ways, which is one reason findings do not always carry over from one model to the other, let alone to people. The outcomes measured are usually infarct size, behaviour and gene or protein expression at fixed time points after the occlusion.
In the 2024 stress study, male rats exposed to weeks of unpredictable mild stressors received daily intraperitoneal Semax or saline. The Semax group was reported to show less anhedonia (measured by sucrose preference), less adrenal enlargement and preserved hippocampal BDNF compared with stressed controls. Neither stress nor Semax changed immobility in the forced-swim test, a reminder that these models do not always agree with each other.11
A 2025 study from a group in Wenzhou, China, reported improved functional recovery in female mice after spinal cord contusion, and used RNA sequencing, network pharmacology and molecular docking to propose the μ-opioid receptor as a Semax target.12 It is one of relatively few Semax papers from outside Russia, and its proposed target has not yet been independently confirmed.
Clinical research on Semax exists, but it is thin by modern standards. Most of it is published in Russian-language journals with only a short English abstract.
A search of ClinicalTrials.gov in September 2026 found no registered Semax trials. There are no large, placebo-controlled, multicentre trials of the kind regulators in Australia, the US or Europe would expect before approving a medicine.
Read as a whole, the literature has recurring weaknesses that any researcher should factor in:
Stronger evidence would look different: replication by laboratories outside the original network, preregistered animal studies with blinded outcome assessment, dose-response data reported in full, and, for any claim about people, randomised placebo-controlled trials registered before they start.
None of this means the findings are wrong. It means they are preliminary. Any claim about Semax that goes beyond "reported in rats" or "reported in a small open study" is running ahead of the evidence.
For in vitro and animal-model work, Semax is normally supplied as a lyophilised (freeze-dried) powder. Like other peptides that contain methionine, it is susceptible to oxidation, which is one reason storage conditions matter; see how to store lyophilised and reconstituted peptides. Titan Peptides supplies Semax 10 mg for laboratory research only. For its closest relative, see Semax vs Selank compared and our Selank research overview.
Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. It combines positions 4 to 7 of the hormone ACTH with a Pro-Gly-Pro tail that slows breakdown by peptidases. It was developed in Russia and is reported to lack the hormonal activity of ACTH. Most research on it involves rat models of stroke, learning and stress.
No. The Drugs@FDA database contains no product containing Semax. The FDA's compounding safety page, current as of April 2026, lists semax among substances previously placed in category 2 over potential safety risks, before the nominations were withdrawn. The FDA said it lacked sufficient information to know whether Semax would cause harm in humans.
Semax is not named in the June 2026 Poisons Standard. Under the Therapeutic Goods Act 1989, goods presented or likely to be taken as being for therapeutic use are therapeutic goods, whatever the label says. Research-grade Semax is not an approved medicine and is supplied for laboratory research only. Our guide to research peptide law in Australia explains the framework.
Mostly experimental stroke in rats, where studies report changes in BDNF signalling and in immune, vascular and neurotransmission gene expression. Smaller bodies of work cover learning tasks, chronic stress models and, recently, spinal cord injury in mice. The human studies are small Russian-language reports in stroke and motor neuron disease, without large controlled trials.
No. Both are synthetic seven-amino-acid peptides from Russian institutes and both end in the same Pro-Gly-Pro tail, but they are built on different parent molecules. Semax is derived from a fragment of the hormone ACTH, while Selank is derived from tuftsin, a short peptide from immunoglobulin G. Their research literatures focus on different models.
Its safety in humans has not been established by the large controlled trials that regulators require. The FDA has said it lacks sufficient safety information to know whether Semax would cause harm and noted a potential immunogenicity risk. The published human studies are small and mostly Russian-language. Titan Peptides supplies Semax for laboratory research only.
Semax and Selank share a Russian origin and the same Pro-Gly-Pro tail, but they are built on different parent peptides and studied in different models. Here is how they compare, study by study.
Selank is a seven-amino-acid analogue of the immune peptide tuftsin, approved in Russia as an anti-anxiety medicine but not in the US or EU. This is what the published studies report, and how far they go.
A laboratory guide to storing lyophilised and reconstituted peptides: freezer temperatures, moisture, oxidation-prone residues, light, freeze–thaw cycles and adsorption to containers.
