Semax: the ACTH(4-10) analogue and its research record

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Prepared by: Research Desk. Sources are linked for verification.

Published 21 October 2026

At a glance

Type: synthetic heptapeptide (7 amino acids) with the sequence Met-Glu-His-Phe-Pro-Gly-Pro
Origin: designed by Moscow research groups at the Institute of Molecular Genetics of the Russian Academy of Sciences and Lomonosov Moscow State University
Research stage: mostly rat and cell studies from Russian groups, a few small Russian-language human studies, and newer independent laboratory work
Regulatory status: not an FDA-approved drug; its nomination for US compounding use was withdrawn

What Semax is

Semax is a short synthetic peptide derived from adrenocorticotropic hormone (ACTH). Its first four residues, Met-Glu-His-Phe, match positions 4 to 7 of ACTH. A Pro-Gly-Pro tripeptide is joined to the end in place of the rest of the natural sequence. For this reason the literature calls it both an "ACTH(4-10) analogue" and "ACTH(4-7)PGP", as in Eremin et al. (2005) and Filippenkov et al. (2020).

The ACTH(4-10) region does not carry the hormone's main effect on the adrenal glands, so analogues of this kind are often described as "noncorticotropic melanocortins". The added Pro-Gly-Pro tail was chosen to make the peptide more resistant to breakdown by enzymes.

Research history

Semax belongs to a family of proline-rich peptides, called glyprolines, studied by the Moscow school of Igor Ashmarin and Nikolai Myasoedov. In a 2005 review in Pathophysiology, Ashmarin et al. argued that peptides carrying a Pro-Gly-Pro motif are far more stable in the body than most regulatory peptides. They grouped Semax with Selank, a related peptide from the same programme, as "hybrid" peptides that join a natural regulatory fragment to a stabilising glyproline tail.

Stability became a research topic of its own. The Myasoedov laboratory published a series of papers on how Semax and its analogues are broken down by aminopeptidases, carboxypeptidases and enzymes in blood and other biological media, including a 2013 study of an acetylated form by Shevchenko et al..

Russian papers describe Semax as a peptide drug used in Russia for cerebrovascular conditions (Sudarkina et al., 2021). That status is national and does not extend to research-grade material sold elsewhere.

Mechanisms studied in preclinical work

Most mechanistic work was done in rats, and most of it comes from the groups that developed the peptide.

Neurotrophins. Dolotov et al. (2003) reported that Semax raised expression of brain-derived neurotrophic factor (BDNF), a protein involved in the growth and survival of nerve cells, in several areas of the rat brain.
Monoamine systems. In rodents, Eremin et al. (2005) found that Semax raised levels of a serotonin breakdown product in the striatum. On its own it did not change dopamine levels, but it markedly enhanced the dopamine release and movement caused by D-amphetamine.
Gene expression after ischaemia. In a rat model of temporary blockage of a brain artery, Filippenkov et al. (2020) used RNA sequencing and found 394 genes expressed differently with Semax than with saline. Genes linked to inflammation were lower and genes linked to neurotransmission were higher. A follow-up protein study by Sudarkina et al. (2021) reported lower levels of MMP-9, c-Fos and active JNK and higher active CREB in the same model.
Stress models. Inozemtseva et al. (2024) compared Semax with Melanotan II, another ACTH(4-10) analogue, in male rats under chronic unpredictable stress. The authors reported that both peptides affected anhedonia-like behaviour and hippocampal BDNF levels and lowered markers of chronic stress load.

These are animal results. Changes in gene or protein expression in rat brain tissue do not show what Semax does in people.

The published research landscape

Two features stand out in the Semax literature.

The first is concentration. A large share of the papers come from a small number of Moscow institutes, and many early reports were published in Russian-language journals or brief communications without full abstracts in PubMed. The same pattern of a dominant originating group appears in our BPC-157 note.

The second is a newer wave of independent laboratory work outside Russia:

Sciacca et al. (2022), at the Institute of Crystallography of Italy's National Research Council in Catania, reported that Semax binds copper ions and interfered with copper-driven aggregation of amyloid beta in cell-free and cell-culture experiments.
Liu et al. (2025), at Wenzhou Medical University in China, studied Semax in a mouse spinal cord injury model and used RNA sequencing and docking to propose the mu-opioid receptor as a possible target. This is a single study and has not been replicated.

Human data are limited to small studies published in Russian. One example is an open-label study of 110 people after ischaemic stroke, which measured plasma BDNF and functional scores (Gusev et al., 2018). It was not randomised or placebo-controlled. We found no large, randomised, placebo-controlled trials of Semax in PubMed, and no systematic review of the human evidence.

Regulatory status

United States. Semax is not an FDA-approved drug. FDA's page on bulk drug substances that may present significant safety risks lists "Semax (heptapeptide)" among nominations that were withdrawn. FDA notes a possible risk of immunogenicity, potential for aggregation, peptide-related impurities, and no or limited safety information for the proposed routes.
Russia. Russian research papers describe Semax as a peptide drug in clinical use in Russia, as noted above.
Elsewhere. We found no marketing authorisation for Semax from the European Medicines Agency or other major Western regulators as of 21 October 2026.

Open research questions

Receptor target. No single receptor has been confirmed. Melanocortin receptors, monoamine systems and, in one recent paper, the mu-opioid receptor have all been proposed.
Independent replication. Core findings on BDNF and ischaemia models come mostly from the originating institutes.
Material identity. Research-grade material should come with identity and purity data. Our guide How to read a peptide COA covers what such reports should contain.

For other compounds studied mainly in animal and cell models, see the notes on AOD-9604 and MOTS-c.

Limitations of the evidence

Most mechanistic data come from rodent models run by the developing groups.
Human studies are small, open-label and published in Russian.
Many early papers are hard to assess from outside because they lack full abstracts or English translations.

Where researchers source it

Purita is a store that lists Semax for laboratory research use only. Its product page carries the label "For Research Use Only. Not for human or animal administration."

Purita product page

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