Neuropeptide Research

Semax: ACTH(4-10) Analog Research Data

A conservative review of Semax: its chemistry and Moscow origin, the rat BDNF and stroke-model data, the small Russian human studies, and where regulators stand in 2026.

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Fact-checked · Reviewed by Remy Research Editorial Board
Update History ▾
October 6, 2026: Initial publication, built from a source-by-source check of the Semax literature, the Russian registration record, FDA's 2026 briefing documents and the July 2026 advisory-committee vote. It separates cell, animal and human evidence, and notes where work comes from the developers' own institute.
Research-use-only framing applied throughout in line with Remy editorial standards.
TL;DR — Research Summary

Semax is a synthetic ACTH(4-10) analog developed in Moscow, registered in Russia as a prescription nasal drop, and studied mostly in rats. In rodent work, much of it from the developers' own institute, Semax raised BDNF and TrkB signalling in the brain and shifted immune, inflammatory and neurotransmission genes after experimental stroke.[1][2] The human evidence is small and Russian-language: a 1997 stroke study, a 2018 rehabilitation study and a 2018 Russian meta-analysis of three placebo-controlled studies. No Semax trial is registered on ClinicalTrials.gov.[3][4][5][6]

Outside Russia, Semax is not an approved medicine. FDA's 2026 review judged the evidence of effectiveness insufficient, and the July 2026 advisory vote concerned pharmacy compounding, not approval.[7][8] Material supplied by Remy Research is for in-vitro laboratory research only — not for human or veterinary use.

Compliance note: this page is a research review, not a treatment guide. It does not provide human-use dosing, therapeutic recommendations, or any clinical-use instructions, and should be read in the same non-therapeutic frame required across Remy's research content.

What Is Semax?

Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP). PubChem lists the free base as C37H51N9O10S, with a molecular weight of about 813.9 g/mol, CAS number 80714-61-0, and PubChem CID 9811102.[9] The registered molecule has a free N-terminus and a free C-terminal acid: it is neither acetylated nor amidated. N-acetylated Semax is a modified analog; in one cell study, acetylation changed the peptide's copper chemistry and removed its protective effect against copper toxicity.[10]

The design starts from adrenocorticotropic hormone (ACTH). Human ACTH(4-10) reads Met-Glu-His-Phe-Arg-Trp-Gly. Semax keeps the first four residues, ACTH(4-7), and replaces Arg-Trp-Gly with the tripeptide Pro-Gly-Pro, which is why it is also written ACTH(4-7)PGP.[11] The Russian label describes Semax as an ACTH(4-10) analog completely devoid of hormonal activity, and a 2024 rat study calls it "noncorticotropic".[12][13]

Salt forms matter when reading papers and certificates. FDA's 2026 briefing lists Semax acetate separately, at about 874 g/mol against 813.9 g/mol for the free base, and notes that Semax is a common name rather than a US adopted name.[7]

Origin: Moscow, 1980s

Semax was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences, working with Lomonosov Moscow State University, under academicians N. F. Myasoedov and I. P. Ashmarin.[14][15] The developers' own 1997 review was subtitled "15 years experience in its design and study", which places the start of the work in the early 1980s.[16]

The Pro-Gly-Pro tail is usually described as a stability feature. Rat-blood studies found Semax more stable than native ACTH(4-10) against several degrading enzymes, although aminopeptidases still cleave its N-terminal residues.[17] With rat brain membranes it had a half-life of over an hour and was cleaved into the shorter fragments His-Phe-Pro-Gly-Pro and Pro-Gly-Pro.[18] After intranasal delivery in rats, labelled Semax reached the brain within minutes, mostly intact at first, and was then degraded rapidly, with Pro-Gly-Pro as the main metabolite.[19] No peer-reviewed human pharmacokinetic study was found.

Proposed Mechanisms and the Evidence Behind Each

Semax has been linked to several pathways, and its receptor is still unknown. The table sorts each proposed mechanism by the kind of evidence behind it.

Semax — Proposed Mechanisms and Evidence
Proposed mechanism What was reported Evidence type
BDNF / TrkB Higher BDNF protein and TrkB activation in rat hippocampus and basal forebrain; rapid rise in BDNF and NGF mRNA in rat glial cultures Animal, cell culture
Neurotrophin genes More transcription of neurotrophins and their receptors in rat cortex after experimental ischaemia Animal
Gene expression Genome-wide shifts in immune, vascular and neurotransmission genes after experimental stroke, with inflammatory genes suppressed Animal
Binding site Specific, calcium-dependent binding to rat basal-forebrain membranes; the receptor itself has not been identified Ex vivo
Melanocortin receptors No direct binding or functional study of Semax at melanocortin receptors was found Not established
Enkephalinase Inhibits enkephalin-degrading enzymes in human serum at micromolar concentrations In vitro
Serotonin, dopamine Raised serotonin turnover and enhanced amphetamine-induced dopamine release in rodents Animal
Copper binding Binds copper(II), reduced copper-induced toxicity in cells and affected copper-driven amyloid-beta aggregation In vitro

The BDNF findings are the most cited. In rat hippocampus, Semax raised BDNF protein about 1.4-fold and TrkB phosphorylation about 1.6-fold, alongside better avoidance learning.[1] In the basal forebrain, BDNF rose within three hours, and the same study reported a specific, calcium-dependent binding site.[20] In rat glial cultures, BDNF and NGF mRNA rose within 30 minutes.[21]

The in-vitro signals are weaker or narrower. Semax inhibits enkephalin-degrading enzymes, but only at micromolar concentrations, and its relevance in a living animal is unknown.[22] In rodents it raised serotonin turnover and, while it did not change dopamine alone, it enhanced amphetamine-induced dopamine release.[23] An Italian group, one of the few non-Russian lines of work, showed that Semax binds copper(II), protects cells against copper toxicity, and changes copper-driven amyloid-beta aggregation in membrane models.[24][25]

The Rat Stroke-Model Evidence

Most of Semax's mechanistic literature comes from rat models of cerebral ischaemia, and most of it from one Moscow research consortium.

1. Neurotrophin Transcription After Permanent Ischaemia (Dmitrieva et al. 2010)

After permanent middle cerebral artery occlusion, Semax increased transcription of neurotrophins and their receptor genes in the ischaemic cortex within hours to days. The authors found the effect of the Pro-Gly-Pro fragment alone to be mainly unspecific.[26]

2. Immune and Vascular Genes (Medvedeva et al. 2014)

A genome-wide analysis in the same model found that immune-response genes made up more than half of the genes Semax altered, with vascular genes also affected.[27]

3. The Ischaemia-Reperfusion Transcriptome (Filippenkov et al. 2020)

In a transient-occlusion model, RNA sequencing found 394 genes differentially expressed with Semax against saline at 24 hours. Inflammatory genes were suppressed and neurotransmission genes activated.[2]

4. Protein-Level Changes (Sudarkina et al. 2021)

At the protein level, 24 hours after transient ischaemia, active CREB rose in subcortical structures including the ischaemic focus, while MMP-9 and c-Fos fell in the adjacent cortex and active JNK fell in both.[28]

The picture is consistent across these papers, but it is rat-only and largely single-consortium. Transcript and protein changes in an animal model are not evidence of clinical benefit.

Human Data: What Exists

The human literature is small, Russian-language and inconsistently reported:

No Semax trial is registered on ClinicalTrials.gov.[6] Of 208 PubMed records on Semax, 47 are tagged as human studies, and none since 2018 is a new stroke trial.[31] FDA's 2026 review judged the evidence of effectiveness insufficient for the uses it evaluated. It did not consider Russian-only references.[7]

What Has Been Published on Safety

There are no long-term human safety data, and no study of Semax combined with Selank was found.

Regulatory Status in 2026

Where Semax stands as of October 6, 2026.
  • Russia. Semax is a registered prescription medicine, sold as 0.1% and 1% nasal drops under certificates reissued in 2025. Its labelled uses centre on ischaemic stroke and cerebrovascular and cognitive conditions, and its nasal forms are on Russia's 2026 Vital and Essential Medicines List.[33][34] FDA notes that the registered Russian product is nasal drops; no registered injectable Semax product was found.[7]
  • United States. Semax is not FDA-approved and is not a component of any approved drug. FDA removed it from Category 2 ("may present significant safety risks") in April 2026 because its nominations were withdrawn.[35] On July 24, 2026 FDA's Pharmacy Compounding Advisory Committee voted 8–5, with one abstention, to recommend adding Semax to the 503A Bulks List, against the recommendation of FDA's reviewers.[36][8] Advisory votes are non-binding, and listing requires notice-and-comment rulemaking; no proposed rule had appeared by October 6, 2026.
  • European Union. There is no centrally authorised Semax product in the EU's Union Register.[37]
  • United Arab Emirates. No UAE registration was found, although the official registry could not be checked conclusively.
  • Sport. Semax is not named on WADA's 2026 or 2027 Prohibited List. Because Semax is approved in Russia, WADA's S0 clause for substances with no approval anywhere does not obviously apply, but the List does not rule on Semax by name. Athletes should get a ruling from their anti-doping organisation rather than assume it is permitted.[38]

What the Semax Literature Does Not Yet Give You

These gaps are not arguments against studying Semax. They are arguments against overselling it.

Where Semax Fits in an RUO Research Catalog

For research use, Semax belongs with the neuropeptide research tools: a defined ACTH(4-10) analog for cell-culture and animal-model work on neurotrophin signalling, gene expression and ischaemia models. Remy Research lists the Genovare Semax 25mg AQ pen and a Selank + Semax 50mg blend pen, both supplied for in-vitro laboratory research only. No published study has examined the two peptides combined. Neither listing is framed for human use, veterinary use or treatment.

For researchers reading this page as a starting point, the most useful adjacent references on this site are the Cerebrolysin neuroprotection review, the peptide primer, the COA and HPLC purity guide, and the Dubai legality brief.

Our Research Standards

This article prioritizes primary literature, regulatory records and FDA's 2026 briefing documents, and notes where findings come from the developers' own institute. Where the human record is thin, we say so directly. No therapeutic, human-use, or veterinary-use claim is made here. Read our editorial policy →

RP
Editorial Review

Editorial Board, Remy Research

The Remy Research Editorial Board reviews Remy's peptide research library, with a focus on analytical verification, clinical-trial interpretation, and compliance-safe scientific communication.

About the editorial team →

Semax Research FAQ

What is Semax?

Semax is a synthetic heptapeptide, Met-Glu-His-Phe-Pro-Gly-Pro (C37H51N9O10S, about 813.9 g/mol, CAS 80714-61-0). It is an analog of the ACTH(4-10) fragment that keeps ACTH residues 4–7 and replaces residues 8–10 with Pro-Gly-Pro. It was developed at the Institute of Molecular Genetics in Moscow with Moscow State University, and Russian sources describe it as devoid of hormonal activity.[9][14]

Is Semax an approved medicine anywhere?

Yes, in Russia, where it is a prescription medicine sold as 0.1% and 1% nasal drops and is on the 2026 Vital and Essential Medicines List. It is not FDA-approved, there is no centrally authorised EU product, and no UAE registration was found.[33][34][7][37]

Did the FDA approve Semax in 2026?

No. On July 24, 2026 an FDA advisory committee voted 8–5, with one abstention, to recommend adding Semax to the list of bulk substances US 503A pharmacies may compound from. FDA's own reviewers had recommended against it. The vote is advisory and is not a drug approval, and no proposed rule had appeared by October 6, 2026.[36][8]

Is Semax on the WADA Prohibited List?

It is not named on the 2026 or 2027 List. WADA's S0 clause covers substances with no government approval for human use, and Semax is approved in Russia, but the List does not rule on Semax by name. Athletes should get a ruling from their anti-doping organisation rather than assume it is permitted.[38]

How is Semax thought to work?

Most mechanistic data come from rats, largely from the developers' institute. Reported findings include higher BDNF and TrkB signalling, more neurotrophin transcription after experimental stroke, and broad shifts in immune, inflammatory and neurotransmission genes. Its specific receptor has not been identified, and no direct evidence ties it to melanocortin receptors.[1][2]

What does the human research on Semax show?

It consists of small, mostly Russian-language studies: a 1997 study of 30 Semax-treated stroke patients against 80 controls, a 2018 rehabilitation study of 110 patients split into Semax and non-Semax subgroups, a 2018 Russian meta-analysis of three placebo-controlled studies with 181 patients, and small fMRI studies in healthy volunteers. No trial is registered on ClinicalTrials.gov, and FDA judged the evidence of effectiveness insufficient.[3][4][5][6]

What safety information has been published on Semax?

The Russian label lists mild nasal irritation with prolonged use and contraindicates use in acute psychiatric states, anxiety disorders, a history of seizures, and pregnancy and lactation. FDA's 2026 review found no published nonclinical toxicity studies and raised immunogenicity concerns for injectable forms. Long-term human safety data are lacking.[12][7]

How does Semax differ from Selank and N-acetyl Semax?

Selank is a different heptapeptide, Thr-Lys-Pro-Arg-Pro-Gly-Pro, from the same Moscow institute; it shares the C-terminal Pro-Gly-Pro, and no published study has examined the two combined. N-acetyl Semax is a modified analog, not the registered drug: in one cell study, N-terminal acetylation changed its copper chemistry and removed its protective effect against copper toxicity. No peer-reviewed human data were found for the acetylated forms.[22][10]

Sources

  1. Dolotov OV, Karpenko EA, Inozemtseva LS, et al. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res. 2006;1117(1):54-60. doi: 10.1016/j.brainres.2006.07.108 · PMID: 16996037 ↩
  2. Filippenkov IB, Stavchansky VV, Denisova AE, et al. Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats. Genes (Basel). 2020;11(6):681. doi: 10.3390/genes11060681 · PMID: 32580520 ↩
  3. Gusev EI, Skvortsova VI, Myasoedov NF, et al. Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study) [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 1997;97(6):26-34. PMID: 11517472 ↩
  4. Gusev EI, Martynov MY, Kostenko EV, et al. The efficacy of semax in the treatment of patients at different stages of ischemic stroke [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118(3 Vyp 2):61-68. doi: 10.17116/jnevro20181183261-68 · PMID: 29798983 ↩
  5. Shmonin AA, et al. Meta-analysis of Semax studies in ischaemic stroke [in Russian]. Vestnik Vosstanovitelnoy Meditsiny (Bulletin of Rehabilitation Medicine). 2018;17(2):81-88. journals.eco-vector.com ↩
  6. ClinicalTrials.gov search for Semax as an intervention, run October 6, 2026 (0 studies). clinicaltrials.gov ↩
  7. U.S. Food and Drug Administration. Briefing document on semax (free base) and semax acetate for the July 2026 Pharmacy Compounding Advisory Committee meeting. fda.gov/media/193348 ↩
  8. McDermott Will & Schulte. Summary of the July 23–24, 2026 PCAC peptide votes, July 27, 2026. mcdermottlaw.com ↩
  9. National Center for Biotechnology Information. PubChem Compound Summary for CID 9811102, Semax (ACTH (4-7), Pro-Gly-Pro-). pubchem.ncbi.nlm.nih.gov/compound/9811102 ↩
  10. Magrì A, Tabbì G, Giuffrida A, et al. 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. 2016;164:59-69. doi: 10.1016/j.jinorgbio.2016.08.013 · PMID: 27586814 ↩
  11. UniProt. P01189 — Pro-opiomelanocortin (POMC_HUMAN), the ACTH precursor sequence. uniprot.org ↩
  12. Vidal Russia drug reference. Semax 0.1% nasal drops: registration LP-No.(009449)-(RG-RU) of March 26, 2025, prescription only; label describes a synthetic ACTH(4-10) analog devoid of hormonal activity. vidal.ru ↩
  13. Inozemtseva LS, Yatsenko KA, Glazova NY, et al. Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress. Eur J Pharmacol. 2024;984:177068. doi: 10.1016/j.ejphar.2024.177068 · PMID: 39442746 ↩
  14. Deigin VI, Poluektova EA, Beniashvili AG, Kozin SA, Poluektov YM. Development of Peptide Biopharmaceuticals in Russia. Pharmaceutics. 2022;14(4):716. doi: 10.3390/pharmaceutics14040716 · PMID: 35456550 ↩
  15. Peptogen (Semax manufacturer). Producer page: development under academicians N. F. Myasoedov (Institute of Molecular Genetics, Russian Academy of Sciences) and I. P. Ashmarin (Lomonosov Moscow State University). semax.ru ↩
  16. Ashmarin IP, Nezavibat'ko VN, Myasoedov NF, et al. A nootropic adrenocorticotropin analog 4-10-semax (15 years experience in its design and study) [in Russian]. Zh Vyssh Nerv Deiat Im I P Pavlova. 1997;47(2):420-430. PMID: 9173745 ↩
  17. Potaman VN, Alfeeva LY, Kamensky AA, et al. N-terminal degradation of ACTH(4-10) and its synthetic analog semax by the rat blood enzymes. Biochem Biophys Res Commun. 1991;176(2):741-746. doi: 10.1016/s0006-291x(05)80247-5 · PMID: 1851003 ↩
  18. Dolotov OV, Zolotarev IuA, Dorokhova EM, et al. The binding of Semax, ACTH 4-10 heptapeptide, to plasma membranes of the rat forebrain basal nuclei and its biodegradation [in Russian]. Bioorg Khim. 2004;30(3):241-246. doi: 10.1023/b:rubi.0000030127.46845.f0 · PMID: 15344653 ↩
  19. Shevchenko KV, Nagaev IIu, Alfeeva LIu, et al. Kinetics of Semax penetration into the brain and blood of rats after its intranasal administration [in Russian]. Bioorg Khim. 2006;32(1):64-70. doi: 10.1134/s1068162006010055 · PMID: 16523722 ↩
  20. Dolotov OV, Karpenko EA, Seredenina TS, et al. Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. J Neurochem. 2006;97 Suppl 1:82-86. doi: 10.1111/j.1471-4159.2006.03658.x · PMID: 16635254 ↩
  21. Shadrina MI, Dolotov OV, Grivennikov IA, et al. Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analog. Neurosci Lett. 2001;308(2):115-118. doi: 10.1016/s0304-3940(01)01994-2 · PMID: 11457573 ↩
  22. Kost NV, Sokolov OIu, Gabaeva MV, et al. Semax and selank inhibit the enkephalin-degrading enzymes from human serum [in Russian]. Bioorg Khim. 2001;27(3):180-183. doi: 10.1023/a:1011373002885 · PMID: 11443939 ↩
  23. Eremin KO, Kudrin VS, Saransaari P, et al. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochem Res. 2005;30(12):1493-1500. doi: 10.1007/s11064-005-8826-8 · PMID: 16362768 ↩
  24. Tabbì G, Magrì A, Giuffrida A, et al. Semax, an ACTH4-10 peptide analog with high affinity for copper(II) ion and protective ability against metal induced cell toxicity. J Inorg Biochem. 2015;142:39-46. doi: 10.1016/j.jinorgbio.2014.09.008 · PMID: 25310602 ↩
  25. Sciacca MFM, Naletova I, Giuffrida ML, et al. Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models. ACS Chem Neurosci. 2022;13(4):486-496. doi: 10.1021/acschemneuro.1c00707 · PMID: 35080861 ↩
  26. Dmitrieva VG, Povarova OV, Skvortsova VI, et al. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. Cell Mol Neurobiol. 2010;30(1):71-79. doi: 10.1007/s10571-009-9432-0 · PMID: 19633950 ↩
  27. Medvedeva EV, Dmitrieva VG, Povarova OV, et al. 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. 2014;15:228. doi: 10.1186/1471-2164-15-228 · PMID: 24661604 ↩
  28. Sudarkina OY, Filippenkov IB, Stavchansky VV, et al. Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion. Int J Mol Sci. 2021;22(12):6179. doi: 10.3390/ijms22126179 · PMID: 34201112 ↩
  29. Lebedeva IS, Panikratova YR, Sokolov OY, et al. Effects of Semax on the Default Mode Network of the Brain. Bull Exp Biol Med. 2018;165(5):653-656. doi: 10.1007/s10517-018-4234-3 · PMID: 30225715 ↩
  30. Panikratova YR, Lebedeva IS, Sokolov OY, et al. Functional Connectomic Approach to Studying Selank and Semax Effects. Dokl Biol Sci. 2020;490(1):9-11. doi: 10.1134/S001249662001007X · PMID: 32342318 ↩
  31. PubMed title/abstract search for "semax", run October 6, 2026 (208 records; 47 tagged Humans). pubmed.ncbi.nlm.nih.gov ↩
  32. Alekseeva GV, Bottaev NA, Goroshkova VV. Use of semax at a follow-up of patients with posthypoxic encephalopathy [in Russian]. Anesteziol Reanimatol. 1999;(1):40-43. PMID: 10199046 ↩
  33. Vidal Russia drug reference. Semax 1% nasal drops: registration LP-No.(010596)-(RG-RU) of June 18, 2025, prescription only. vidal.ru ↩
  34. Government of the Russian Federation. Order No. 3867-r of December 18, 2025 approving the Vital and Essential Medicines List (in force February 24, 2026); group N06BX lists the Semax substance in liquid forms for nasal use. publication.pravo.gov.ru ↩
  35. U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks (Semax listed under "nominated but withdrawn"; page modified April 22, 2026). fda.gov ↩
  36. U.S. Food and Drug Administration. July 23–24, 2026: Meeting of the Pharmacy Compounding Advisory Committee (Docket FDA-2025-N-6895). fda.gov ↩
  37. European Commission. Union Register of medicinal products for human use (searched October 6, 2026; no Semax entry). ec.europa.eu ↩
  38. World Anti-Doping Agency. 2027 Prohibited List (in force January 1, 2027), class S0 Non-Approved Substances; Semax is not named on the 2026 or 2027 List. wada-ama.org ↩

For catalog details, see the Genovare Semax 25mg AQ pen and the Selank + Semax blend pen. For compliance context, continue to the Dubai legality brief and the research standards page.

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