Semax is a synthetic heptapeptide built around a four-amino-acid fragment of adrenocorticotropic hormone (ACTH), residues 4 through 7, with a three-amino-acid Pro-Gly-Pro sequence added to the end. Its full sequence is Met-Glu-His-Phe-Pro-Gly-Pro, commonly abbreviated MEHFPGP. The compound was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences in Moscow, as part of a broader program into short regulatory peptides derived from larger signaling hormones. Unlike the natural ACTH(4-10) fragment it is based on, which peptidases clear from circulation within minutes, Semax carries the added C-terminal tripeptide to resist that breakdown, giving researchers a longer working window for study in cell and animal models. Published work spans decades of Russian- and English-language literature, concentrated on rodent cerebral ischemia models, hippocampal neurotrophin signaling, and, more recently, melanocortin-pathway comparisons.
| Attribute | Detail |
|---|---|
| Name | Semax, a synthetic ACTH(4-7)-Pro-Gly-Pro heptapeptide |
| Sequence | Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP) |
| Class | Synthetic neuropeptide, ACTH(4-10) fragment analog |
| Origin | Developed at the Institute of Molecular Genetics, Russian Academy of Sciences, Moscow |
| C-terminal modification | Pro-Gly-Pro tripeptide extension appended to the ACTH(4-7) core for enzymatic resistance |
| What studies examine | BDNF and TrkB receptor expression, neurotrophin gene transcription, brain protein expression profiles, melanocortin-pathway comparisons |
| Model systems used | Rat hippocampus and frontal cortex, cerebral ischemia-reperfusion models, cultured neural tissue |
| Regulatory status | Registered as a pharmaceutical product in Russia; not an approved drug in the United States |
| Form supplied | Lyophilized powder, research use only |
What is Semax and where does its structure come from?
ACTH is a 39-amino-acid hormone, and the segment spanning positions 4 through 7, Met-Glu-His-Phe, is one of several short fragments of the parent hormone that researchers in the melanocortin field have studied independently of ACTH's role in adrenal signaling. Semax extends that four-residue core with Pro-Gly-Pro at the C-terminus, producing a seven-residue peptide structurally distinct from either the native ACTH(4-10) fragment or free Pro-Gly-Pro alone. A short linear fragment like ACTH(4-7) is degraded almost immediately by circulating and tissue peptidases, so the proline-containing cap was intended to slow that breakdown and extend the window for study in cell culture and animal models.
What role does the Pro-Gly-Pro extension play in enzymatic stability?
Pro-Gly-Pro is itself studied as a distinct molecule in the literature, separate from Semax, because proline-flanked tripeptides of this kind resist cleavage by common aminopeptidases and prolyl endopeptidases that would otherwise rapidly break down a short linear peptide. Several research groups working on Semax have examined the parent heptapeptide alongside free Pro-Gly-Pro in the same experiments, to separate what each piece contributes. Dmitrieva and colleagues compared Semax and Pro-Gly-Pro directly in a rat cerebral ischemia model and reported that both molecules activated transcription of neurotrophin and neurotrophin-receptor genes, though not always to the same degree (Dmitrieva et al., 2010), a design Stavchanskii and colleagues extended in a model of incomplete global ischemia, again treating Semax and its C-terminal fragment as separate variables affecting neurotrophin and receptor gene expression in rat brain tissue (Stavchanskii et al., 2011). This recurring side-by-side design is a reason the C-terminal extension is treated as mechanistically relevant rather than an inert stabilizing tag.
What have rodent and cell studies measured for BDNF and TrkB expression?
A substantial portion of the Semax literature centers on brain-derived neurotrophic factor (BDNF) and its receptor TrkB. Dolotov and colleagues administered Semax to rats and measured BDNF protein and trkB gene expression in hippocampal tissue, reporting changes in both relative to untreated animals and describing Semax as an ACTH(4-10) analog with measurable effects on this signaling pair (Dolotov et al., 2006). A separate study by Agapova and colleagues tracked the time course of BDNF and nerve growth factor (NGF) gene expression in rat hippocampus and frontal cortex after Semax administration, reporting that the two neurotrophin genes followed distinct temporal patterns rather than moving together, suggesting Semax engages more than one neurotrophin pathway (Agapova et al., 2008). Expanding past this pair, Sudarkina and colleagues profiled brain protein expression in a rat ischemia-reperfusion model after Semax administration, reporting protein-level changes consistent with the gene-transcription effects above and framing this as confirmatory evidence at the protein level for effects previously reported mainly at the mRNA level (Sudarkina et al., 2021). This body of work is largely why Semax is discussed as a tool for studying neurotrophin-pathway gene regulation in the rodent brain rather than as a single-receptor pharmacological agent.
How does Semax relate to the melanocortin receptor system?
Because Semax is built from a fragment of ACTH, a precursor hormone that also gives rise to melanocortin peptides such as alpha-MSH, it sits adjacent to the melanocortin receptor literature even though its own studies focus on neurotrophin signaling rather than classical melanocortin receptor pharmacology. A 2024 study by Inozemtseva and colleagues examined Semax directly alongside Melanotan II, a separate synthetic ACTH(4-10)-related analog studied for melanocortin receptor engagement, testing both peptides in a rat model of chronic unpredictable stress and reporting antidepressant-like and antistress behavioral measures for both (Inozemtseva et al., 2024). That study helps place Semax relative to other ACTH-derived research peptides: it shares a structural origin with melanocortin receptor agonists without being classified primarily as a melanocortin receptor ligand itself. For a peptide studied specifically for melanocortin receptor engagement, see what is PT-141.
How does Semax compare to other heptapeptides studied at the same institute?
Semax was developed alongside Selank, another short synthetic peptide from the same Moscow research program, and the two are frequently discussed together in review literature because of their shared origin and overlapping study designs. This article focuses on Semax's structure, stability design and expression-level findings; for a side-by-side look at how Selank and Semax differ in sequence and proposed mechanism, see Selank vs Semax.
What is Semax's regulatory status?
Semax is registered as a pharmaceutical product in Russia, authorized in a nasal-drop formulation for specific indications under the Russian regulatory framework. That registration is specific to Russia; Semax has not been evaluated or approved by the United States Food and Drug Administration. Homegrown Peptides supplies Semax strictly as a research-use-only laboratory reagent, not as a pharmaceutical product.
Handling notes
Semax is supplied as a lyophilized powder for research use. It should be stored per the certificate of analysis and reconstituted using standard bench technique and concentration math, bench math for preparing a solution for an assay, not guidance for use in any subject. See peptide half-life explained for background on why the C-terminal extension above, and cold storage, affect solution stability. Confirm identity and purity from the lot-specific certificate of analysis before use in an assay. Lot-specific specs for research-grade Semax are posted on our Semax lot page.
Frequently asked questions
Is Semax the same molecule as ACTH?
No. Semax is a synthetic seven-amino-acid peptide built from ACTH residues 4 through 7 (Met-Glu-His-Phe), with a Pro-Gly-Pro extension at the C-terminus. It is not the full 39-amino-acid ACTH hormone.
What does the Pro-Gly-Pro extension do?
Published studies describe the Pro-Gly-Pro tripeptide as a design element intended to slow enzymatic breakdown of the short ACTH(4-7) core, and several studies have examined Semax and free Pro-Gly-Pro side by side to compare their separate contributions to measured gene- and protein-expression effects in rat brain tissue.
What animal models have been used to study Semax?
Rat hippocampus and frontal cortex tissue, rat models of cerebral ischemia and ischemia-reperfusion, and a rat model of chronic unpredictable stress, alongside cultured neural tissue.
How is Semax related to Selank?
Both were developed at the Institute of Molecular Genetics in Moscow and are often discussed together in review literature. See Selank vs Semax for a direct comparison of sequences and proposed mechanisms.
Has Semax been studied in humans?
The studies summarized in this article are cell culture and rodent studies examining gene expression, protein expression and behavioral measures in animal models. This article describes laboratory research models, not clinical evidence, and nothing here describes use of this compound in any subject.
How is Semax supplied for laboratory use?
As a lyophilized powder for research use only, sold by lot with an accompanying certificate of analysis.
References
- 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. PubMed 16996037.
- 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. Cell Mol Neurobiol. 2010;30(1):71-9. PubMed 19633950.
- Stavchanskiĭ VV, Tvorogova TV, Botsina AYu, Skvortsova VI, Limborskaia SA, Miasoedov NF, Dergunova LV. The effect of semax and its C-end peptide PGP on expression of the neurotrophins and their receptors in the rat brain during incomplete global ischemia. Mol Biol (Mosk). 2011;45(6):1026-35. PubMed 22295573.
- Agapova TYu, Agniullin YaV, Silachev DN, Shadrina MI, Slominsky PA, Shram SI, Limborska SA, Myasoedov NF. Effect of semax on the temporary dynamics of brain-derived neurotrophic factor and nerve growth factor gene expression in the rat hippocampus and frontal cortex. Mol Gen Mikrobiol Virusol. 2008;(3):28-32. PubMed 18756821.
- 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. PubMed 34201112.
- Inozemtseva LS, Yatsenko KA, Glazova NY, Kamensky AA, Myasoedov NF, Levitskaya NG, Grivennikov IA, Dolotov OV. 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. PubMed 39442746.
Research use only. Homegrown Peptides products are for laboratory research and are not for human or animal use. Nothing in this article is medical advice.
