Semax and cerebral ischaemia: what the ACTH(4-10) literature examined

Semax is a registered medicine in Russia. It is approved nowhere else — not by Health Canada, not by the FDA, not by the EMA — and that one fact frames everything below.

In English-language discussion Semax is usually a cognitive peptide. That is the later thread. The original one was cerebral ischaemia, and it is the reason the molecule was designed at all.

Where the compound came from

Semax was developed at the Institute of Molecular Genetics in Moscow, part of the Russian Academy of Sciences, by a team led by Nikolai Myasoedov. It is conventionally called an ACTH(4-10) analogue, and that name is looser than it sounds.

The sequence is Met-Glu-His-Phe-Pro-Gly-Pro. The first four residues are lifted from adrenocorticotropic hormone. The trailing Pro-Gly-Pro is not — it was added deliberately. Native ACTH(4-10) is cleared from plasma almost immediately, and the proline-rich tail is what buys the molecule enough time to be studied at all. The result is a heptapeptide that retains the neurotropic activity attributed to the parent fragment while losing the hormone's adrenal activity. The design work is Ashmarin and colleagues, 1995, and like most of the foundational material it is a Russian publication.

What the published ischaemia work measured

Three papers carry the modern mechanistic literature. All three measure molecules in animals, not recovery in people.

VEGF signalling under focal ischaemia. Medvedeva and colleagues examined Semax and its C-terminal fragment Pro-Gly-Pro in experimental focal ischaemia of the rat brain, and reported changes in the expression of VEGF family genes and their receptors (PMID 22772900). VEGF governs the growth of new blood vessels, which is a sensible place to look in tissue whose blood supply has been interrupted. The endpoint is gene expression in rat brain.

Neurogenesis and apoptosis genes. Dergunova and colleagues examined Semax effects on the expression of genes involved in neurogenesis and apoptosis in rat brain. The same class of readout — transcription, not function.

Specific binding, and BDNF. Dolotov and colleagues reported that Semax binds specifically and raises levels of brain-derived neurotrophic factor (PMID 16635254). This is the most-cited mechanistic result in the modern literature, and it is the more interesting one, because specific binding is a stronger claim than a change in a transcript count and relatively few peptides in this category have it. BDNF itself sits at the centre of neuronal survival and synaptic plasticity biology, which is why a compound that moves it attracts attention from two directions at once.

Note what those three papers are not. None of them is a clinical trial, and none of them reports a neurological outcome in a human being. The mechanistic literature is rodent and in vitro work on gene expression and a neurotrophin.

The clinical literature you probably cannot read

Semax is registered in Russia on the strength of Russian clinical research in ischaemic stroke and cognitive disorders, accumulated over several decades. That body of work is real, and it is also the weakest part of the case as it reaches a reader here.

It is published largely in Russian-language journals. Very little of it is indexed in a form a Western reader can retrieve, and almost none of it has been replicated outside that tradition. There are no Western phase-three trials to compare it against, no regulatory review in Canada, the United States or the EU that has examined the dossier, and consequently no independent read on either effect size or safety. None of the Russian clinical work appears in the reference list at the foot of this article, because the citations carried here are the mechanistic papers. Treat the clinical claim as something that exists in one research tradition and has not been tested against another.

About the word in the title

This article carries a disease name. That is a liability worth stating outright rather than writing around.

What the literature did was induce ischaemia experimentally in animals and then measure brain tissue. 'Examined in rat models of cerebral ischaemia' is a statement about a set of experiments. It is not a statement about what happens to a person who has had a stroke, and nothing on this page should be read that way. Stroke is a medical emergency with established hospital care, and this compound is not part of it anywhere outside Russia.

Where the evidence stops

Two further limits are easy to lose. Rodent ischaemia models produce a clean, timed, experimentally induced injury, while human stroke is heterogeneous in cause, location and timing. And a change in the expression of a gene is several steps removed from a change in how a brain works — it is the beginning of a mechanistic account, not the end of one.

What this means for a research question

The literature is most developed where the question is transcriptional: what happens to VEGF, neurogenesis and apoptosis genes in brain tissue after an ischaemic insult. It is thinnest exactly where most readers want it to be strongest, which is human outcome.

For the parallel Russian neuropeptide, developed at the same institute and registered in Russia under the same pattern, see Selank for Stress Response Research. Nothing here is medical, dosing, or therapeutic guidance.

Semax is supplied here as Semax. Janoshik-verified by HPLC with mass-spec identity confirmation; 100% synthetic. The measured purity for each lot is stated on its product page. For laboratory research use only.

Common questions

Is Semax an approved stroke treatment? It is a registered medicine in Russia, where its indications include cerebrovascular and cognitive conditions. It is approved nowhere else. No Canadian, American or European regulator has cleared it for anything, and material sold here is a research chemical, not a medicine.

Why is the research so hard to find? Because most of it was published in Russian, in Russian journals, often before online indexing was routine. The mechanistic papers cited below are the accessible end of the literature. The clinical end mostly is not, and a compound whose strongest claims sit in untranslated work is a compound whose claims are hard to check.

Is Semax really an ACTH(4-10) analogue? Partly. Four of its seven residues come from that fragment; the Pro-Gly-Pro tail is synthetic and was added for stability. The hormonal activity of the parent molecule is not retained, which was the point of the design.

What has been established about the mechanism? Specific binding and an increase in BDNF levels (PMID 16635254), and changes in VEGF family and neurogenesis or apoptosis gene expression in rat brain (PMID 22772900, PMID 24708833). What has not been established is how those findings connect to a neurological outcome in a person.

Selected Research References

1. Dergunova LV, Dmitrieva VG, Filippenkov IB, et al. The Effect of Semax on the Expression of Genes Involved in Neurogenesis and Apoptosis in Rat Brain. Genes. 2014.
2. Dolotov OV, Karpenko EA, Inozemtseva LS, et al. Semax, an Analog of Adrenocorticotropin (4-10), Binds Specifically and Increases Levels of Brain-Derived Neurotrophic Factor. Journal of Neurochemistry. 2006;97(s1):82-86. pubmed.ncbi.nlm.nih.gov/16635254
3. Medvedeva EV, Dmitrieva VG, Povarova OV, et al. Effect of Semax and Its C-Terminal Fragment Pro-Gly-Pro on the Expression of VEGF Family Genes and Their Receptors in Experimental Focal Ischemia of the Rat Brain. Journal of Molecular Neuroscience. 2013;49(2):328-333. pubmed.ncbi.nlm.nih.gov/22772900
4. Ashmarin IP, Nezavibatko VN, Levitskaya NG, et al. Design and Investigation of an ACTH(4-10) Analog Lacking D-amino Acids and Hydrophobic Radicals. Neuroscience Research Communications. 1995. (Foundational Russian publication on Semax development.)

All products sold by NovaEvum are for research and laboratory use only. They are not intended for human or animal consumption, diagnosis, treatment, cure, or prevention of any disease.