Semax Research, Specifications & Scientific Information

Introduction

Semax is a seven-residue synthetic peptide with an unusual pedigree. Its first four residues are lifted directly from adrenocorticotropic hormone, and the three that follow — proline, glycine, proline — were appended for a single structural reason: to slow the enzymatic cleavage that clears the natural fragment within minutes ^[5]. It was developed at the Institute of Molecular Genetics in Moscow and is registered as a pharmaceutical product in the Russian Federation, marketed there as an intranasal preparation since the 1990s.

That history shapes the evidence in a way this page has to state plainly. The clinical literature is real, indexed in PubMed, and in places controlled — and it is almost entirely in Russian, confined to a small number of neurology journals, and in several cases carries no digital object identifier at all. The experimental literature runs the other way: mostly in English, mostly recent, and unusually molecular for a compound of this vintage, built on genome-wide transcriptional and proteomic profiling in rat stroke models. Both are set out below, kept apart, and labelled for what they are.

What Is Semax?

Semax is a synthetic heptapeptide, sequence Met-Glu-His-Phe-Pro-Gly-Pro, written MEHFPGP in single-letter code. The first four residues are the 4–7 fragment of adrenocorticotropic hormone; the trailing Pro-Gly-Pro tripeptide has no counterpart in the parent hormone and was added synthetically.

It belongs to a family of short regulatory peptides developed in the Soviet Union and the Russian Federation from the 1980s onward, of which Selank is the other well-known member. Both carry the same C-terminal Pro-Gly-Pro motif on a different parent sequence, and the motif is the family resemblance.

Two things about its status need saying at the outset, because they are routinely conflated. First, Semax is a registered pharmaceutical product in the Russian Federation, which is a fact about Russian regulatory law and nothing else. Second, it has not been approved by the U.S. Food and Drug Administration for any indication, and no marketing application for it is on record in the United States. There is no ClinicalTrials.gov record of it as an investigational product. A registration in one jurisdiction establishes nothing in another, and neither one establishes anything about research-grade material supplied for laboratory work.

The parent hormone, ACTH, is a melanocortin: it acts at the melanocortin receptor family. Semax is described in the literature as a melanocortin derivative on structural grounds ^[9], but that is a statement about where the sequence came from, not a characterised receptor interaction. No binding affinity at a named receptor has been published for the heptapeptide.

Semax Specifications

Semax is the ACTH(4-7) tetrapeptide Met-Glu-His-Phe extended at the C-terminus by the tripeptide Pro-Gly-Pro. The parent fragment ACTH(4-10) is a short-lived sequence in plasma; the Pro-Gly-Pro extension is the structural device that slows enzymatic cleavage, and it is the same C-terminal motif carried by Selank, the other peptide of this Russian series. The identifiers shown here are the records held by PubChem (CID 9811102), which carries CAS registry number 80714-61-0 and FDA/NCATS UNII code I5FAL2585H for the free peptide. The molecular formula and mass correspond to the unmodified seven-residue free acid; material supplied as an acetate or trifluoroacetate salt carries a different measured mass, which is one reason a catalogue figure and a certificate of analysis for a given lot are not interchangeable. Any figure on this page is a reference value: the certificate of analysis supplied with a laboratory order is the record for a given lot.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does Semax Work?

The honest answer is that the molecular starting point is not established, and the literature is candid about it. A genome-wide study published in 2014 opens by saying that the molecular mechanisms underlying the peptide's action remain obscure ^[7], and nothing published since has closed that gap with a receptor and an affinity constant.

What exists instead is a downstream description. The peptide is associated with changes in neurotrophin expression — brain-derived neurotrophic factor and nerve growth factor, together with the BDNF receptor TrkB — and, in models of focal cerebral ischaemia, with shifts in immune and vascular gene expression. Those are the observations. Whether they follow from a receptor interaction, from an effect of one of the cleavage fragments, or from something else entirely is not resolved in the published work.

One structural point is settled. The parent ACTH(4-10) fragment is short-lived in biological media; the Pro-Gly-Pro extension slows its breakdown, and the fragments that appear when the heptapeptide is degraded have been characterised directly ^[5]. That stability is the reason the molecule is studiable at all, and it is also why the tripeptide Pro-Gly-Pro itself has been investigated as a separate agent.

Semax Mechanism of Action

Animal research

The mechanistic evidence base is rodent work, and it should be read as rodent work.

Neurotrophins in the hippocampus. A single intranasal application of 50 µg/kg in rats produced, at maximum, a 1.4-fold increase in BDNF protein and a 1.6-fold increase in TrkB tyrosine phosphorylation in the hippocampus, with a 3-fold increase in exon III BDNF messenger RNA and a 2-fold increase in trkB messenger RNA. The same animals showed more conditioned avoidance reactions than controls ^[4]. The authors' own framing is a suggestion, not a conclusion: that the peptide acts on hippocampal function by modulating the BDNF/TrkB system.

Region specificity. An hour after a single 50 µg/kg intranasal application in male Wistar rats, expression of both Bdnf and Ngf rose in the hippocampus; Bdnf also rose in the brainstem and cerebellum, while Ngf expression fell in the frontal cortex ^[6]. The direction of change is not uniform across the brain, which is a detail that summaries of this compound routinely drop.

Transcriptional response under ischaemia. In rats subjected to permanent middle cerebral artery occlusion, genome-wide profiling of cortical tissue at three and twenty-four hours found the peptide's effect concentrated in the immune system: at twenty-four hours, genes of the immune response made up more than half of all transcripts whose expression it altered, with immunoglobulin and chemokine genes the most prominent groups. Vascular-system genes were also affected — twenty-four at three hours, twelve at twenty-four hours — including genes associated with endothelial development and migration, smooth muscle cell migration and vasculogenesis ^[7].

Protein-level corroboration. In a transient occlusion model, active CREB was raised in subcortical structures including the focus of ischaemic damage, while MMP-9 and c-Fos fell in the adjacent frontoparietal cortex and active JNK fell in both tissues, twenty-four hours after occlusion ^[9]. The authors read this as suppression of inflammatory and cell-death processes alongside activation of recovery-associated signalling.

Scale of the transcriptional effect. A 2024 RNA-Seq study of the penumbra-associated frontal cortex found 3,774 differentially expressed genes attributable to ischaemia alone at twenty-four hours; 1,539 were differentially expressed under Semax, and for 1,171 genes associated with immune and neurosignalling pathways the peptide significantly reduced the distortion caused by ischaemia. A structurally related peptide, ACTH(6-9)PGP, behaved more similarly to Semax than differently from it at that time point ^[11].

Findings in this section were observed in rats. Nothing in them establishes anything about humans.

What Is Semax Being Researched For?

The published research divides cleanly, and the division is worth keeping in view:

• Acute ischaemic stroke — Russian clinical studies from the 1990s onward, including a controlled comparison in the acute hemispheric setting ^[1] and a later study of rehabilitation timing ^[8].
• Cerebrovascular insufficiency — a Russian clinical study in 187 participants across stages of the condition ^[3].
• Experimental cerebral ischaemia — rat permanent and transient middle cerebral artery occlusion models, profiled at the transcriptome and protein level ^{[7, 9, 11]}.
• Neurotrophin regulation in normal brain — rat hippocampus, brainstem, cerebellum and frontal cortex ^{[4, 6]}.
• Rodent models of chronic stress — a chronic unpredictable stress paradigm in male rats ^[10].
• Peptide stability and degradation — characterisation of cleavage products in rat cell cultures and on plasma membranes ^[5].

None of that is research into, or evidence about, research-grade material supplied for laboratory use.

Human Research on Semax

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

Four limitations apply to everything in this section and are not repeated under each study. The trials were conducted and published in the Russian Federation; the full texts are in Russian and this summary rests on the English abstracts indexed in PubMed; the earlier reports carry no digital object identifier and predate modern trial-registration practice; and none of the work has been replicated outside Russia.

Controlled study in acute hemispheric ischaemic stroke, 1997

Population. 30 participants in the acute period of hemispheric ischaemic stroke, against a control group of 80 participants with strokes of comparable severity and location receiving conventional therapy ^[1].

Endpoint and duration. Clinical rating scales for severity and neurological deficit, with electroencephalographic monitoring with mapping and repeated analysis of somatosensory evoked potentials. Courses of five and ten days ^[1].

Result. The report describes an influence on the rate at which damaged neurological functions were restored, with greater regression of general cerebral and focal disturbances, motor disturbances especially. The amounts reported as most effective were 12 mg daily in strokes of moderate severity and 18 mg daily in severe strokes ^[1].

Limitations. Thirty participants against a non-randomised comparison group more than twice its size, reported in 1997 without a registered protocol, and no effect size is recoverable from the indexed abstract.

Immunobiochemical analysis in acute ischaemic stroke, 1999

Population and design. A retrospective comparative clinical and immunobiochemical analysis in the acute period of ischaemic stroke ^[2].

Result. The authors report a shift in the balance of circulating mediators toward interleukin-10 and tumour necrosis factor alpha relative to interleukin-8 and C-reactive protein, which they interpret as activation of anti-inflammatory post-ischaemic reactions ^[2].

Limitations. Retrospective, no participant count in the indexed abstract, and the inflammatory-mediator classification used in the report does not match current usage — tumour necrosis factor alpha is not generally treated as an anti-inflammatory mediator. This citation is included because it is part of the record, not because its interpretation stands unchallenged.

Cerebrovascular insufficiency, 2005

Population. 187 participants at different stages of cerebrovascular insufficiency, diagnosed on neurological and neuropsychological examination, ultrasonic dopplerography, rheo- and encephalography, electrocardiography, brain magnetic resonance imaging and fundus examination ^[3].

Endpoint. Tolerability, clinical status on neurological scales, and complications over the course of the condition ^[3].

Result. The report describes clinical improvement, stabilisation of disease progression, and a reduced rate of stroke and transient ischaemic attacks over the observation period, with a low proportion of side-effects including in older participants ^[3].

Limitations. No control-group description, no randomisation, and no numerical result in the indexed abstract. Words such as "significant" appear without the figures that would support them.

Rehabilitation timing and plasma BDNF after ischaemic stroke, 2018

Population. 110 participants after ischaemic stroke — 43 men, 67 women, mean age 58.0 ± 9.7 years — divided into early (89 ± 9 days) and late (214 ± 22 days) rehabilitation groups, each subdivided by whether the peptide was administered ^[8].

Endpoint and duration. Plasma BDNF concentration, motor performance on the British Medical Research Council scale, and Barthel index score, followed over five months. The regimen was two ten-day courses of 6000 µg per day with a twenty-day interval ^[8].

Result. Plasma BDNF rose and remained elevated across the study period regardless of when rehabilitation began. Among participants not receiving the peptide, higher plasma BDNF correlated with earlier rehabilitation. Barthel index improvement was faster and its final value higher where the peptide was administered and BDNF was high; the effect on motor deficit was smaller. The correlation between plasma BDNF and Barthel score was modified by rehabilitation timing ^[8].

Limitations. This is the most informative of the clinical reports and still falls short of what would be expected of a registrational trial: 110 participants, no stated blinding or placebo control in the abstract, correlational analysis carrying much of the argument, and a biomarker — plasma BDNF — whose relationship to brain BDNF is itself contested.

Preclinical Research on Semax

Animal research

Beyond the ischaemia and neurotrophin work described under mechanism, one rodent behavioural study is worth setting out because it is recent, in English, and reports a negative result alongside positive ones.

Adult male Sprague-Dawley rats were exposed to chronic unpredictable stress and given daily intraperitoneal injections of saline or 60 nmol/kg of either Semax or Melanotan II. Chronic administration of either peptide reversed or substantially attenuated stress-induced anhedonia measured by sucrose preference, suppression of body-weight gain, adrenal hypertrophy, and the fall in hippocampal BDNF. In the forced swim test, neither the stress procedure nor either peptide changed the duration of immobility ^[10].

The forced-swim null result matters. It is the test most often used to claim antidepressant-like activity, and reporting that it showed nothing, in the same paper as four positive measures, is the kind of completeness that makes the rest of the data easier to trust.

The study also sits the compound beside Melanotan II — another ACTH(4-10) analogue, from a quite different research tradition — and finds broadly similar behaviour in this paradigm. That is a mechanistic hint about the melanocortin origin of both sequences rather than a finding about either compound on its own.

Findings described in this section were observed in rats, in one sex, under one stress paradigm. Nothing in them establishes anything about humans.

Other Areas of Semax Research

In vitro research

The one substantial body of non-animal work concerns what happens to the molecule itself.

Using a peptide isotopically labelled at every amino acid residue, degradation was followed in the presence of plasma membranes and of glial and neuronal cell cultures prepared from rat basal forebrain. The dominant processes were cleavage of the N-terminal Met-Glu and of the C-terminal Gly-Pro, with pentapeptides forming as the principal intermediates. The pattern of resulting fragments differed between glial and neuronal cultures ^[5].

Two consequences follow, and both are relevant to anyone reading the rest of the literature. The first is that the heptapeptide does not persist unchanged in the presence of the tissues it is studied in, so any account of its activity has to contend with a mixture of parent peptide and fragments. The second is that Pro-Gly-Pro, the C-terminal tripeptide added to stabilise the molecule, is itself released — and Pro-Gly-Pro has its own published literature as a regulatory peptide. Whether some part of what is attributed to the heptapeptide belongs to its fragments is an open question in the primary sources, not a settled one.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Semax vs Related Compounds

The comparison most often made is with Selank, and the two are frequently discussed as a pair because they came out of the same laboratory and share a structural motif. They are not variants of one another.

Shared motif

Both carry the C-terminal tripeptide Pro-Gly-Pro, appended for stability rather than inherited from a natural sequence. That is the whole of the structural resemblance.

Parent sequences

Semax is built on ACTH(4-7), a fragment of adrenocorticotropic hormone. Selank is built on tuftsin, a fragment of the immunoglobulin G heavy chain. Different parents, different literatures.

Research literatures

The Semax literature is dominated by neurotrophin expression and experimental cerebral ischaemia. The Selank literature is dominated by GABAergic pharmacology and anxiolytic models. No study compares the two head to head on any measure, and none is described here.

Modified variants

N-acetyl Semax, and amidated forms of it, are distinct compounds with their own identifiers and a much smaller published literature. Nothing established for the unmodified heptapeptide transfers to them automatically.

Regulatory position

Both are registered pharmaceutical products in the Russian Federation. Neither is approved by the U.S. Food and Drug Administration for any indication. Approval is specific to a compound, an indication and a jurisdiction.

No comparison of effect between these compounds is made on this page.

Chemical & Molecular Characteristics

Semax is an unmodified seven-residue peptide with a free N-terminus and a free C-terminal carboxyl group. PubChem carries it as compound identifier 9811102, with CAS registry number 80714-61-0 and FDA/NCATS UNII code I5FAL2585H. The molecular formula recorded there is C37H51N9O10S and the average mass 813.9 g/mol.

Three points are worth drawing out of those figures.

The sulfur is the N-terminal methionine. It is the only sulfur-containing residue in the sequence, and it is the residue cleaved first in the degradation work described above ^[5]. Methionine is also the residue most prone to oxidation in a peptide of this composition, which is why analytical characterisation of a given lot matters more here than the catalogue formula does.

The Pro-Gly-Pro extension is synthetic. ACTH(4-10) ends Met-Glu-His-Phe-Arg-Trp-Gly. Semax keeps only the first four of those residues and replaces the rest with Pro-Gly-Pro. It is therefore not a truncation of the natural hormone but a chimera, and the two arginine- and tryptophan-bearing positions that carry most of the melanocortin receptor pharmacology of ACTH are absent from it. That is the structural reason not to assume melanocortin receptor activity from the name alone.

Salt form changes the measured mass. The formula and mass above are for the free peptide. Material supplied as an acetate or trifluoroacetate salt has a different measured mass and a different peptide content by weight. A catalogue figure and a certificate of analysis are not interchangeable, and only the latter describes a specific lot.

Analytical Specifications

Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.

Frequently Asked Questions

Scientific References

1. Gusev EI, Skvortsova VI, Miasoedov NF, et al.. [Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)] Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova; 1997. PMID 11517472
2. Miasoedova NF, Skvortsova VI, Nasonov EL, et al.. [Investigation of mechanisms of neuro-protective effect of semax in acute period of ischemic stroke] Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova; 1999. PMID 10358912
3. Gusev EI, Skvortsova VI, Chukanova EI. [Semax in prevention of disease progress and development of exacerbations in patients with cerebrovascular insufficiency] Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova; 2005. PMID 15792140
4. 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. PMID 16996037 doi:10.1016/j.brainres.2006.07.108
5. Zolotarev YA, Dolotov OV, Inozemtseva LS, et al.. Degradation of the ACTH(4-10) analog Semax in the presence of rat basal forebrain cell cultures and plasma membranes Amino acids; 2006. PMID 16773243 doi:10.1007/s00726-006-0328-8
6. Agapova TY, Agniullin YV, Shadrina MI, et al.. Neurotrophin gene expression in rat brain under the action of Semax, an analogue of ACTH 4-10 Neuroscience letters; 2007. PMID 17353092 doi:10.1016/j.neulet.2007.02.042
7. 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. PMID 24661604 doi:10.1186/1471-2164-15-228
8. Gusev EI, Martynov MY, Kostenko EV, et al.. [The efficacy of semax in the tretament of patients at different stages of ischemic stroke] Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova; 2018. PMID 29798983 doi:10.17116/jnevro20181183261-68
9. 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. PMID 34201112 doi:10.3390/ijms22126179
10. 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 European journal of pharmacology; 2024. PMID 39442746 doi:10.1016/j.ejphar.2024.177068
11. Filippenkov IB, Shpetko YY, Stavchansky VV, et al.. ACTH-like Peptides Compensate Rat Brain Gene Expression Profile Disrupted by Ischemia a Day After Experimental Stroke Biomedicines; 2024. PMID 39767736 doi:10.3390/biomedicines12122830

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Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.

Related laboratory reagent: Semax specifications and lot documentation