Semax Canada: ACTH(4-10) Analogue & BDNF Research Guide

By the ThePeptide Research Team · Compound reference guide · Semax 10mg is in stock · Last updated September 2026

Semax is a synthetic heptapeptide with the amino-acid sequence Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP), formed by joining the ACTH(4–7) fragment of adrenocorticotropic hormone to the C-terminal tripeptide Pro-Gly-Pro. It is one of the most heavily investigated compounds in the Russian neuropeptide research programme, where it has been studied since the 1990s for effects on brain-derived neurotrophic factor (BDNF) and its receptor TrkB, and in rodent models of cerebral ischaemia. Semax occupies an unusual position in the peptide literature: it is a registered medicine in the Russian Federation, yet it has never been approved by Health Canada or the United States Food and Drug Administration, and the bulk of its clinical record is published in Russian-language journals. This guide sets out what the indexed literature actually reports, with PubMed identifiers throughout.

What is Semax?

Semax is a synthetic seven-residue peptide, Met-Glu-His-Phe-Pro-Gly-Pro, constructed by attaching the glyproline tripeptide Pro-Gly-Pro to the C-terminus of the ACTH(4–7) fragment of adrenocorticotropic hormone. In the primary literature it is written interchangeably as Semax, ACTH(4–7)PGP and ACTH(4–10) analogue, and it is characterised as a non-hormonal melanocortin derivative — that is, a fragment analogue that does not carry the corticotropic activity of the parent hormone. It is studied predominantly by Moscow groups working at the Institute of Molecular Genetics, now part of the National Research Centre “Kurchatov Institute” — notably the Myasoedov, Limborska and Dergunova laboratories, whose names recur on almost every transcriptomic paper cited below.

What is Semax's amino-acid sequence and molecular formula?

Semax has the sequence Met-Glu-His-Phe-Pro-Gly-Pro (single-letter MEHFPGP), the molecular formula C₃₇H₅₁N₉O₁₀S, a molecular weight of approximately 813.93 g/mol, and CAS number 80714-61-0. Its PubChem compound record is CID 9811102, filed under the systematic name ACTH (4-7), Pro-Gly-Pro-. The full chemical name is L-methionyl-L-α-glutamyl-L-histidyl-L-phenylalanyl-L-prolylglycyl-L-proline. As a research material it is supplied as a lyophilized powder and is characterised, like any synthetic peptide, by reversed-phase HPLC for purity and by mass spectrometry for identity against the expected monoisotopic mass. If peptide nomenclature is unfamiliar, our beginner's guide to what peptides are covers sequence notation and how synthetic analogues are named.

How is Semax different from ACTH(4–10)?

Semax differs from native ACTH(4–10) by the substitution of its final three residues: where ACTH(4–10) reads Met-Glu-His-Phe-Arg-Trp-Gly, Semax reads Met-Glu-His-Phe-Pro-Gly-Pro. The conserved N-terminal ACTH(4–7) core (Met-Glu-His-Phe) is retained; the Arg-Trp-Gly segment, which carries much of the melanocortin-receptor pharmacophore of the parent hormone, is replaced by the proline-rich Pro-Gly-Pro tripeptide. That design is the reason the compound is described across the Russian literature as non-hormonal: the Filippenkov group's 2025 paper explicitly labels both ACTH(4–7)PGP and the related ACTH(6–9)PGP as "non-hormonal" peptides (PMID 40650034). The proline-flanked C-terminus is also the structural feature that distinguishes the glyproline family from ordinary linear fragments.

Does Semax affect BDNF and TrkB?

Yes — the BDNF/TrkB axis is the single best-characterised mechanism reported for Semax, and it comes from two 2006 papers by Dolotov and colleagues. In Brain Research, a single Semax exposure produced a maximal 1.4-fold increase in BDNF protein in the rat hippocampus, alongside elevated TrkB phosphorylation and TrkB mRNA, with the authors concluding that the peptide's cognitive effects are mediated through hippocampal BDNF/TrkB signalling (PMID 16996037). In Journal of Neurochemistry, the same group reported that Semax binds specifically in rat basal forebrain tissue and raises BDNF protein levels there (PMID 16635254). Those are the two anchor citations for essentially every downstream claim about Semax and neurotrophins.

What did the rat cerebral ischaemia studies find?

The rat middle cerebral artery occlusion literature is where the Semax evidence base is densest, and it is overwhelmingly transcriptomic rather than behavioural. Dmitrieva and colleagues reported that Semax activated Bdnf, TrkC and TrkA transcription in rat cortex at 3 hours after permanent MCAO, Nt-3 and Ngf at 24 hours, and Ngf at 72 hours, while the Pro-Gly-Pro control acted "mainly unspecific" (PMID 19633950). Medvedeva and colleagues' genome-wide analysis found that immune-response genes made up over 50% of all Semax-altered transcripts at 24 hours after pMCAO, with 24 vascular-system genes changed at 3 hours and 12 at 24 hours (PMID 24661604).

The RNA-Seq generation

Filippenkov and colleagues moved the same model to RNA-Seq, identifying 394 differentially expressed genes (greater than 1.5-fold) in rat brain 24 hours after transient MCAO under Semax versus saline, with inflammation-related expression suppressed and neurotransmission-related expression activated — a pattern the authors framed as compensation for ischaemia-induced disruption (PMID 32580520). A companion proteomic study reported upregulated active CREB in subcortical structures and downregulated MMP-9 and c-Fos in adjacent frontoparietal cortex at 24 hours (PMID 34201112). The 2025 follow-up compared Semax with ACTH(6–9)PGP across brain regions of differing ischaemic damage, reporting that the peptides reduced ischaemia-induced disturbance for close to two thousand differentially expressed genes in frontal cortex, while ACTH(6–9)PGP amplified disruption in 152 inflammation-associated genes (PMID 40650034).

How does Semax affect dopamine and serotonin in rodents?

Published rodent work reports modulatory rather than direct effects on monoamines. Eremin and colleagues, working with Rayevsky's group and Finnish collaborators at Tampere, found that Semax raised striatal 5-hydroxyindoleacetic acid (5-HIAA) content by 25% at 2 hours, did not by itself alter baseline extracellular dopamine, but "dramatically enhanced" the effect of d-amphetamine on both extracellular dopamine and locomotor activity (PMID 16362768). Separately, a 2004 report in Neuroscience and Behavioral Physiology examined Semax in the MPTP model of dopaminergic lesion (PMID 15341218). The monoamine literature is therefore smaller and less consistent than the neurotrophin literature, and should be weighted accordingly.

What has in-vitro neuronal work shown?

Direct cellular electrophysiology and imaging work on Semax is sparse but continuing. In a 2025 Bulletin of Experimental Biology and Medicine study, Kolbaev, Sharonova and Skrebitsky applied Semax at 1 µM to rat brain slices and dissociated cells and reported a significant increase in the frequency of spontaneous intracellular calcium fluctuations in the CA1 pyramidal layer of the hippocampus, with no appreciable effect on proton-induced calcium responses in cerebellar granule cells (PMID 41171324). The authors read this as evidence that the peptide's activity operates through hippocampal pathways rather than through suppression of acid-sensing ion channels. That is a mechanistic detail worth noting because it narrows, rather than broadens, the plausible mechanism.

What does the Russian clinical literature on Semax report?

The PubMed-indexed clinical record for Semax is small, Russian-authored, and concentrated in one journal. Gusev, Skvortsova, Myasoedov and colleagues reported a 1997 study in the S.S. Korsakov Journal of Neurology and Psychiatry of 30 patients in the acute period of hemispheric ischaemic stroke against 80 controls receiving standard care, combining clinical rating scales with electrophysiological monitoring; the article is in Russian (PMID 11517472). A 2018 study from Gusev, Martynov, Kostenko and colleagues in the same journal enrolled 110 patients (43 men, 67 women, mean age 58.0 ± 9.7 years), stratified by early versus late intervention, and tracked plasma BDNF alongside Barthel index and motor performance, reporting positive correlation between BDNF levels and Barthel scores (PMID 29798983). An early 1996 Russian-language report on human electroencephalography sits at the front of this literature (PMID 8679991).

Why is Semax approved in Russia but not in Canada?

Semax is a registered medicine in the Russian Federation and appears on the Russian government's List of Vital and Essential Medicines, while no Canadian or United States regulator has ever authorised it — an asymmetry driven by where the evidence was generated and which regulator reviewed it. The Russian dossier rests largely on domestically conducted trials published in Russian-language journals; Health Canada and the FDA have not reviewed that dossier, and neither has issued a market authorisation. Health Canada's position is that peptides of this general class are regulated as prescription drugs and that unauthorised drug products are illegal to sell in Canada. Our explainer on whether peptides are legal in Canada sets out the federal framework in detail.

Read the Health Canada public advisory on peptides bought online before drawing conclusions from any of the above: Health Canada advisory, 9 April 2026.

How strong is the Semax evidence base, honestly?

The honest answer is that Semax has an unusually deep mechanistic literature and an unusually shallow independent clinical one, and the two should not be conflated. Four structural weaknesses are worth naming. First, concentration of authorship: Myasoedov, Limborska and Dergunova appear on most of the major transcriptomic papers, so replication is largely internal rather than independent. Second, language and access: substantial clinical material is Russian-language, and some of it is indexed only by title and abstract. Third, model narrowness: MCAO in rats dominates, and behavioural endpoints are thinner than gene-expression endpoints. Fourth, no North American regulatory review has ever tested the dossier. Our peptides ranked by evidence tier guide explains how to weigh exactly this kind of profile.

None of that makes the published findings false. It means they are what they are: a coherent rodent mechanistic story plus a national clinical literature that has not been independently reproduced outside its country of origin. Claims circulating online tend to compress that distinction; our fact-check of viral peptide studies works through how that compression happens.

How does Semax compare to other research peptides on evidence quality?

Semax sits in a different evidence category from the metabolic and repair peptides most researchers encounter first, because its strongest data are transcriptomic and its clinical data are geographically confined. The comparison below is about the shape of each evidence base, not about relative merit or any suggestion of use. A compound with hundreds of rodent gene-expression endpoints and one national clinical literature is a different research proposition from one with a large multinational trial programme, and the difference matters when planning an experiment or reading a claim.

How is Semax identity and purity confirmed in a laboratory?

Synthetic Semax is verified the same way any solid-phase-synthesised peptide is: reversed-phase HPLC with UV detection establishes chromatographic purity, and mass spectrometry confirms that the measured mass matches the expected value for C₃₇H₅₁N₉O₁₀S at approximately 813.93 g/mol. A batch-specific Certificate of Analysis should carry the chromatogram, the mass-spec trace, the lot number printed on the vial, and the identity of the testing laboratory. For material we do stock, batch COAs are published on our lab results page before the lot goes on sale. If you need to validate a lot from any source independently, our guide to where to get research peptides tested in Canada lists the analytical options.

How is lyophilized Semax stored as a research material?

Sealed, unopened vials of lyophilized peptide are generally held frozen, protected from light and from moisture, following the documentation supplied with the specific lot. Semax is a short, proline-containing peptide with a single methionine residue, and methionine side chains are susceptible to oxidation, which is the usual reason peptide storage guidance emphasises sealed containers and minimal air exposure. This page gives no preparation, solution, dilution or handling-for-use instructions of any kind; qualified laboratories follow their own institutional protocols. For the general principles of lyophilized-peptide stability, see our complete research-peptide stability and storage guide.

Is Semax available from ThePeptide.ca?

Yes. Semax 10mg is stocked at $64.99 CAD and supplied strictly as a laboratory research material. The current lot is CS-sem10-0625, independently assayed by Janoshik Analytical — the manufacturer’s third-party laboratory — at 99.138% purity by reversed-phase HPLC with 11.32 mg of measured peptide content per vial, published under Janoshik ref #200391 and readable on that laboratory’s own system at verify.janoshik.com. That is a manufacturer result rather than a certificate issued to us: the lot is with Testides in Toronto for our own confirmatory HPLC, and it is shown as pending on our lab results page until that certificate is released. This article still exists as a literature reference rather than a product page, because Semax comes up constantly in questions about neurotrophin research and because the accurate picture — deep Russian mechanistic literature, registered in one country, unapproved in ours — is rarely stated plainly anywhere else. Nothing about stocking the compound changes that record: Semax is not approved by Health Canada or the FDA and is not for human or veterinary use. The research library index covers the rest of the catalogue.

References

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 Research. 2006;1117(1):54–60. PMID: 16996037. DOI: 10.1016/j.brainres.2006.07.108.
2. 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. Journal of Neurochemistry. 2006;97(Suppl 1):82–86. PMID: 16635254. DOI: 10.1111/j.1471-4159.2006.03658.x.
3. Dmitrieva VG, Povarova OV, Skvortsova VI, Limborska SA, Myasoedov NF, Dergunova LV. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. Cellular and Molecular Neurobiology. 2010;30(1):71–79. PMID: 19633950. DOI: 10.1007/s10571-009-9432-0.
4. 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. PMID: 24661604. DOI: 10.1186/1471-2164-15-228.
5. 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. 2020;11(6):681. PMID: 32580520. DOI: 10.3390/genes11060681.
6. 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. International Journal of Molecular Sciences. 2021;22(12):6179. PMID: 34201112. DOI: 10.3390/ijms22126179.
7. Filippenkov IB, Shpetko YY, Ales DA, et al. Genes that associated with action of ACTH-like peptides with neuroprotective potential in rat brain regions with different degrees of ischemic damage. International Journal of Molecular Sciences. 2025;26(13):6256. PMID: 40650034. DOI: 10.3390/ijms26136256.
8. Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grivennikov IA, Myasoedov NF, Rayevsky KS. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochemical Research. 2005;30(12):1493–1500. PMID: 16362768. DOI: 10.1007/s11064-005-8826-8.
9. Kolbaev SN, Sharonova IN, Skrebitsky VG. The effect of peptide Semax, an ACTH(4-10) analogue, on intracellular calcium dynamics in rat brain neurons. Bulletin of Experimental Biology and Medicine. 2025;179(4):416–420. PMID: 41171324. DOI: 10.1007/s10517-025-06501-z.
10. Levitskaya NG, Sebentsova EA, Andreeva LA, Alfeeva LY, Kamensky AA, Myasoedov NF. The neuroprotective effects of Semax in conditions of MPTP-induced lesions of the brain dopaminergic system. Neuroscience and Behavioral Physiology. 2004;34(4):399–405. PMID: 15341218. DOI: 10.1023/B:NEAB.0000018752.59465.28.
11. Gusev EI, Skvortsova VI, Miasoedov NF, Nezavibat'ko VN, Zhuravleva EIu, Vanichkin AV. Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study). Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 1997;97(6):26–34. PMID: 11517472. [Article in Russian]
12. Gusev EI, Martynov MY, Kostenko EV, Petrova LV, Bobyreva SN. The efficacy of semax in the treatment of patients at different stages of ischemic stroke. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2018;118(3):61–68. PMID: 29798983. DOI: 10.17116/jnevro20181183261-68.
13. Koroleva MV, Meizerov EE, Nezavibatko VN, Kamenskiy AA, Dubynin VA. Effect of the heptapeptide Semax on the human electroencephalogram. Biulleten' Eksperimental'noi Biologii i Meditsiny. 1996;121(1):116–117. PMID: 8679991. [Article in Russian]
14. Health Canada. Think twice before injecting peptides bought online: unauthorized products can seriously harm you. Public advisory, 9 April 2026. recalls-rappels.canada.ca