Semax

Semax is a synthetic heptapeptide developed in Russia as an analogue of the adrenocorticotropic hormone fragment ACTH(4-7), extended with a Pro-Gly-Pro tail. It is studied for neurotrophic signaling and in models of brain injury.

Last reviewed 2026-10-25 by the PeptideWiki editorial team. Editorial policy.

Overview

Semax was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. It combines the ACTH(4-7) fragment, Met-Glu-His-Phe, with a C-terminal Pro-Gly-Pro sequence that was added to improve resistance to enzymatic breakdown. Short ACTH fragments had attracted interest because they appeared to affect attention and learning in animals without the hormonal activity of full-length ACTH on the adrenal cortex.

Research on semax has been conducted largely by Russian groups and published mainly in Russian-language or regional journals. The literature includes rodent models of cerebral ischemia, gene-expression studies, and clinical studies carried out in Russia, where semax is reported to be registered as a medicine. Independent replication elsewhere is limited. In July 2026 the FDA's Pharmacy Compounding Advisory Committee voted to recommend adding semax to the 503A bulk drug substances list, but that vote is advisory and no final FDA action has been announced.

Compare: Selank vs Semax.

Structure

Semax is a linear heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP). Residues 1 to 4 correspond to positions 4 to 7 of human ACTH, and residues 5 to 7 form the Pro-Gly-Pro extension shared with selank. The N-terminal methionine is susceptible to oxidation to methionine sulfoxide, which is the most common degradation pathway to watch for. Research material is typically supplied as an acetate or trifluoroacetate salt. Acetylated or amidated variants exist in the research market and are distinct compounds.

Mechanism

The mechanism of semax is not fully defined. Studies from the developing institute report that it increases expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in rodent brain tissue, and that it alters expression of genes related to inflammation and vascular function after experimental ischemia. Effects on dopaminergic and serotonergic systems have also been described. Semax does not appear to act as a classical ACTH agonist at the adrenal melanocortin receptor. A specific high-affinity receptor for semax has not been established, so these findings describe downstream changes rather than a confirmed primary target.

Research

Experimental cerebral ischemia

A substantial part of the semax literature uses rodent models of stroke, such as permanent or transient occlusion of cerebral arteries. These studies report changes in neurotrophin expression, inflammatory genes and markers of tissue injury in treated animals. The work is preclinical and comes mainly from a small number of Russian laboratories. Translation of these findings to human stroke outcomes has not been demonstrated in large international trials.

Neurotrophin and gene expression studies

Semax has been examined in transcriptomic and molecular studies in rodent brain tissue and in cultured neural cells. Reported effects include increased BDNF and TrkB expression and broad shifts in genes related to immune response and vascular signaling. These findings are frequently cited, but most come from the same research network, and how they relate to any functional outcome remains an open question.

Learning and attention in animals

Earlier work on ACTH fragments, and later work on semax itself, used rodent learning and memory tasks. Some studies report improved performance in specific behavioral paradigms. Behavioral results of this kind are sensitive to test conditions and have not been consistently replicated by independent groups. They are animal findings and do not establish cognitive effects in people. Independent, preregistered studies would be needed to judge whether these effects are robust.

Clinical studies in Russia

Semax has been studied clinically in Russia, including in patients after ischemic stroke, and it is reported to be registered as a medicine there. Published clinical studies are generally small, frequently open-label or with limited methodological detail, and often available only in Russian. Human evidence meeting current international trial standards is limited. Independent trials with blinded outcome assessment and adequate sample sizes have not been reported in the international literature.

Regulatory status

Semax is not approved by the FDA for any use. In July 2026 the FDA's Pharmacy Compounding Advisory Committee voted to recommend adding semax to the Section 503A bulk drug substances list; FDA's own reviewers had recommended against, the vote is advisory, and FDA must act through notice-and-comment rulemaking before any change takes effect. No final FDA action has been announced. Semax is reported to be registered as a medicine in Russia. For sport, check the current WADA Prohibited List.

Status changes often. See the regulatory tracker for dated updates.

Quality and identity testing

A semax certificate of analysis should confirm identity by mass spectrometry against the expected mass shown on this page and report HPLC purity with a chromatogram. The key compound-specific pitfall is methionine oxidation: the sulfoxide appears as a +16 Da species and often elutes slightly earlier on reverse-phase HPLC, so the MS data should address it. The certificate should also make clear whether the material is plain semax or an N-acetyl or C-amidated variant, and should report the salt form and net peptide content.

Open Semax in the sequence analyzer to see the expected [M+H]⁺ and multiply charged ions for an MS identity check.

For a walkthrough of each section of a certificate, see how to read a COA.

Storage and stability

Store lyophilized semax sealed at -20 °C or below, protected from light and moisture. Because the N-terminal methionine oxidizes readily, minimize exposure to air, avoid prolonged storage in solution, and consider using degassed buffers for solution work. Allow vials to warm to room temperature before opening, aliquot any prepared solution, and avoid repeated freeze-thaw cycles.

Download the Semax data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.

Latest research

Frequently asked questions

Related compounds

• Selank

  Selank is a synthetic heptapeptide developed in Russia, built from the immunomodulatory tetrapeptide tuftsin extended with a Pro-Gly-Pro tail. It is studied mainly for effects on anxiety-related behavior and immune signaling.

• DSIP

  DSIP (delta sleep-inducing peptide) is a nonapeptide first isolated in the 1970s from the blood of rabbits in which sleep had been induced. Its physiological role and receptor remain unresolved, and human evidence is limited.

• Pinealon

  Pinealon is a synthetic tripeptide (Glu-Asp-Arg) from Vladimir Khavinson's group in St. Petersburg, one of their short peptide bioregulators. It has been studied mainly in cell and animal models of neural aging and stress, with evidence mostly from that group.

References

1. PubMed: all indexed literature on Semax
2. ClinicalTrials.gov: registered studies mentioning Semax