What is Semax?
Semax is a synthetic heptapeptide, Met-Glu-His-Phe-Pro-Gly-Pro, that joins the adrenocorticotropic hormone fragment ACTH(4-7) to a C-terminal Pro-Gly-Pro tripeptide (PubChem CID 9811102). The Pro-Gly-Pro tail affords increased resistance to peptidases, and the peptide is described as having no hormonal activity (Radchenko et al., 2025). Published work on the Semax peptide covers neurotrophin signaling, rodent brain ischemia models, monoamine neurochemistry, amyloid and copper chemistry, and a small number of imaging studies in healthy volunteers.
Semax is a registered medicine in Russia, where it is included in the government's list of vital and essential drugs for medical application (Radchenko et al., 2025). The Semax that Disguised Alpha sells is a research-grade lyophilized peptide for laboratory use. It is not that medicine, it is not intended for any clinical use, and it is not for use in people.
Semax reference data
| Property | Value |
|---|---|
| Name | Semax |
| Aliases | ACTH(4-7)-Pro-Gly-Pro, MEHFPGP (PubChem CID 9811102) |
| Sequence | Met-Glu-His-Phe-Pro-Gly-Pro (H-MEHFPGP-OH), free N-terminus and C-terminal acid (PubChem CID 9811102) |
| Peptide class | ACTH(4-10) analog heptapeptide |
| Molecular formula | C₃₇H₅₁N₉O₁₀S |
| Molecular weight | 813.94 g/mol |
| CAS number | 80714-61-0 |
| Form | Lyophilized powder |
| Size carried | 10MG |
| Testing | Third-party tested, with the certificate for each lot published on the product page and in the COA portal |
Formula, molecular weight, CAS number and peptide class are from the Compound Information section of the Semax product page, and the 10 mg size is the labeled amount shown there; sequence and aliases are from PubChem (CID 9811102, which lists 813.9 g/mol). Confirm identity and measured content against your lot's certificate.
What the research covers
Published work on Semax falls into six areas. Each summary below states the model used. The imaging studies used a Semax drug preparation, not the research material sold here.
Design, stability and metabolism
A review of glyproline peptides, the family that includes Semax and Selank, reported that Pro-Gly-Pro-containing peptides are about as stable as major pharmacological preparations (Ashmarin et al., 2005). In rats given tritium-labeled Semax by nasal administration, labeled material reached the brain within 2 minutes, about 80 percent of it as intact Semax, and the peptide was then degraded rapidly, with Pro-Gly-Pro predominating among the products (Shevchenko et al., 2006). Incubated with nerve cells, Semax broke down mainly to His-Phe-Pro-Gly-Pro and Pro-Gly-Pro (Zolotarev et al., 2006).
Neurotrophin signaling and neuronal cultures
Tritium-labeled Semax bound rat basal forebrain membranes in a specific, reversible, calcium-dependent manner with a dissociation constant of about 2.4 nM, and nasal administration raised BDNF protein in the basal forebrain at 3 hours but not in the cerebellum (Dolotov et al., 2006a).
In rat hippocampus, a single application raised BDNF protein up to 1.4-fold and trkB tyrosine phosphorylation 1.6-fold, roughly tripled exon III BDNF mRNA, doubled trkB mRNA and increased conditioned avoidance responses (Dolotov et al., 2006b). In primary rat basal forebrain cultures, Semax increased survival of cholinergic neurons about 1.5 to 1.7-fold and stimulated choline acetyltransferase activity at 100 nM (Grivennikov et al., 2008).
Brain ischemia models and gene expression
After permanent middle cerebral artery occlusion in rats, Semax raised cortical transcription of Bdnf, TrkC and TrkA at 3 hours, Nt-3 and Ngf at 24 hours and Ngf at 72 hours. Its effect was selective for ischemic cortex, while the Pro-Gly-Pro fragment alone acted mainly nonspecifically (Dmitrieva et al., 2010). A genome-wide study in the same model found that Semax predominantly enhanced immune-system genes, more than half of the genes it altered at 24 hours, with immunoglobulin and chemokine genes most prominent; 24 vascular-system genes changed at 3 hours (Medvedeva et al., 2014).
Monoamine systems and stress models
In mice, Semax raised striatal tissue 5-hydroxyindoleacetic acid by about 25 percent at 2 hours and gradually raised extracellular levels over 1 to 4 hours, without changing dopamine on its own. Given before D-amphetamine, it enhanced amphetamine-induced striatal dopamine release and locomotor activity (Eremin et al., 2005). In male rats under chronic unpredictable stress, repeated systemic administration of Semax reversed or attenuated anhedonia in the sucrose preference test, suppression of body-weight gain, adrenal hypertrophy and the fall in hippocampal BDNF, while forced-swim immobility did not change. Melanotan II was tested in parallel (Inozemtseva et al., 2024).
Amyloid and copper-binding studies
Semax forms a stable complex with copper(II). In biophysical, membrane-model and cell-viability assays, it prevented formation of amyloid-β:copper complexes and showed anti-aggregating and protective properties, especially in the presence of copper (Sciacca et al., 2022). A follow-up study reported that Semax extracts copper(II) from copper-amyloid-β species, lowers copper-catalyzed reactive oxygen species production and protects SH-SY5Y cells from the resulting oxidative stress (Tomasello et al., 2025).
In APPswe/PS1dE9 transgenic mice, a one-month course of Semax brought several open field, novel object recognition and Barnes maze measures closer to wild-type values and reduced amyloid plaque counts in cortex and hippocampus (Radchenko et al., 2025).
Imaging studies in healthy volunteers
Two resting-state functional MRI studies measured brain network activity, not clinical outcomes. In 24 volunteers given Semax or placebo by nasal administration, the Semax group showed a larger medial frontal subcomponent of the default mode network (Lebedeva et al., 2018). A study of 52 participants comparing Semax, Selank and placebo reported group differences in connectivity between the right amygdala and right temporal cortex (Panikratova et al., 2020).
Key studies
- Eremin KO, et al. "Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents." Neurochem Res. 2005. PMID 16362768. DOI 10.1007/s11064-005-8826-8. Mouse striatum: monoamines, alone and with D-amphetamine.
- Dolotov OV, 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. PMID 16635254. DOI 10.1111/j.1471-4159.2006.03658.x. Rat brain membrane binding and basal forebrain BDNF.
- Dolotov OV, et al. "Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus." Brain Res. 2006. PMID 16996037. DOI 10.1016/j.brainres.2006.07.108. Rat hippocampus: BDNF and trkB protein and mRNA, avoidance conditioning.
- Medvedeva EV, 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. Rat focal ischemia: genome-wide cortical transcription.
- Panikratova YR, et al. "Functional Connectomic Approach to Studying Selank and Semax Effects." Dokl Biol Sci. 2020. PMID 32342318. DOI 10.1134/S001249662001007X. Resting-state fMRI in 52 healthy participants.
- Sciacca MFM, et al. "Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models." ACS Chem Neurosci. 2022. PMID 35080861. DOI 10.1021/acschemneuro.1c00707. In vitro: copper-amyloid-β complexes, aggregation and cell viability.
- Inozemtseva LS, 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. PMID 39442746. DOI 10.1016/j.ejphar.2024.177068. Male rats under chronic stress: sucrose preference, adrenal weight, hippocampal BDNF.
- Radchenko AI, et al. "The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer's Disease." Acta Naturae. 2025. PMID 41479572. DOI 10.32607/actanaturae.27808. APPswe/PS1dE9 transgenic mice: behavior and amyloid plaques.
Handling and storage of lyophilized Semax
General laboratory practice for this material:
- Store the lyophilized powder at -20°C, protected from light, until use (storage guidance on the product page).
- Let the sealed vial reach room temperature before opening so moisture does not condense on the powder.
- The N-terminal residue is methionine, whose side chain oxidizes readily, so limit exposure to air, light and oxidizers.
- Semax binds copper(II) tightly enough to pull it from copper-amyloid-β complexes (Tomasello et al., 2025), so trace metals or chelators can change what is in solution.
- Peptidases cleave Semax quickly (Zolotarev et al., 2006). In serum-containing media or tissue preparations, confirm stability over the experiment, as one neuronal culture study did by HPLC (Grivennikov et al., 2008).
- After reconstitution, keep solutions at 2 to 8°C and protected from light, and split stock into single-use aliquots to avoid freeze/thaw cycles.
- Record the lot number and keep its certificate with your notes. For quantitative work, use the measured content on the certificate rather than the label mass.
Frequently asked questions
What is Semax?
Semax is a synthetic heptapeptide, Met-Glu-His-Phe-Pro-Gly-Pro (PubChem CID 9811102). Rodent studies link it to BDNF and trkB expression in the hippocampus (Dolotov et al., 2006b), and it is also studied in ischemia models, neuronal culture and in vitro amyloid chemistry.
What does the Semax peptide sequence mean?
Met-Glu-His-Phe are positions 4 to 7 of adrenocorticotropic hormone, and the Pro-Gly-Pro tail adds resistance to peptidases (Radchenko et al., 2025). That is why papers describe Semax both as ACTH(4-7)-Pro-Gly-Pro and as an analogue of ACTH(4-10) (Dolotov et al., 2006a).
How does Semax compare with Selank?
Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro, PubChem CID 11765600) shares only the Pro-Gly-Pro tail with Semax. Both inhibited enkephalin-degrading enzymes in human serum in vitro (Kost et al., 2001), and one imaging study tested them side by side (Panikratova et al., 2020). See our Selank research guide.
Why do sources list slightly different molecular weights for Semax?
Our product page lists 813.94 g/mol for C₃₇H₅₁N₉O₁₀S, and PubChem rounds the same formula to 813.9 g/mol. Salt forms such as acetate add mass, so for quantitative work use the formula and measured content on your lot's certificate.
How should Semax powder be stored?
Keep the lyophilized powder at -20°C and protected from light. After reconstitution, store the solution at 2 to 8°C, protected from light, and avoid freeze/thaw cycles, as listed on the product page.
Where can researchers buy Semax?
Disguised Alpha sells it for laboratory research, third-party tested with the certificate published on the product page: Semax (10MG).
Related compounds and guides
- Selank and its research guide
- Semax & Selank, a lyophilized blend of both peptides, and its research guide
- Melanotan 2, tested alongside Semax in a rat chronic stress study, and its research guide
- COA portal: every published certificate, by lot
This product is for research use only. It has not been evaluated for safety or effectiveness in humans. Not for human consumption. All products are intended for laboratory research purposes only.