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Research / Semax peptide review
Reference review

Semax peptide: structure, mechanism and published research

Null Bio Lab Research Desk · Last reviewed October 18, 2026 · Research use only

Scope. This article summarises published laboratory literature for readers working with Semax as a research reagent. It gives no dosing, administration or usage guidance, and nothing here is a statement about any use in humans or animals. Semax is not an authorised medicine in the EU or US.
Key facts
  • Sequence: Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP)
  • Design: ACTH(4–7) fragment + C-terminal Pro-Gly-Pro (PGP)
  • Monoisotopic mass: 813.35 Da; [M+H]+ ≈ 814.36 (average mass 813.9)
  • Main research areas: neurotrophin gene expression, ischaemia-model transcriptomics, monoamine neurochemistry
  • Status: not an authorised medicine in the EU or US (to our knowledge)

What Semax is

Semax is a synthetic heptapeptide, Met-Glu-His-Phe-Pro-Gly-Pro, built from a fragment of adrenocorticotropic hormone (ACTH) joined to a Pro-Gly-Pro tail.1 Early papers call it an analogue of ACTH(4–10), whose native sequence is Met-Glu-His-Phe-Arg-Trp-Gly; Semax keeps the first four residues and replaces the rest with PGP, which is why later papers describe it as ACTH(4–7)PGP.2 Full-length ACTH has 39 residues, so Semax contains only a small piece of the hormone. The published research on the molecule is centred on the nervous system.

Structure and stability

Short peptides are broken down quickly by peptidases in serum and tissue. Biochemical work found that Semax is degraded by rat serum enzymes and examined which inhibitors slow that process, which is the background for the stabilising PGP motif.3 PGP is itself a small peptide with reported activity, so the groups studying Semax repeatedly test the intact molecule against PGP alone to separate their effects.1

A coordination-chemistry study reports that Semax binds copper(II) ions with high affinity and tested protective effects against metal-induced toxicity in cell culture.4 That is a chemistry observation relevant to handling and formulation, not a statement about activity in living organisms.

Neurotrophin and BDNF studies

Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are among the most studied signalling pairs in neuroscience, so measuring their transcripts is a common first step when testing a peptide. The Semax literature returns to them often:

  • Hippocampus. A study titled “Semax, an analog of ACTH(4–10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus” reports changes in both transcripts.2
  • Basal forebrain. A companion paper reports specific binding of Semax in rat basal forebrain tissue and increased BDNF levels there.5
  • Glial cultures. Rapid induction of neurotrophin mRNAs by Semax was reported in rat glial cell cultures, a simplified system without whole-animal physiology and the setting closest to in-vitro reagent use.6
  • Ischaemia model. In rat permanent middle cerebral artery occlusion, Semax was reported to raise transcription of several neurotrophin and receptor genes in the ischaemic cortex (notably Bdnf and TrkC early, Nt-3 and Ngf later). The PGP fragment alone gave overlapping but less selective effects, and the authors note the study measured mRNA only.1

Transcriptome studies

Genome-wide analyses widened the focus beyond neurotrophins. In rat focal ischaemia, Semax was reported to affect expression of genes related to the immune and vascular systems,7 and a later study examined its protective properties at the transcript level following cerebral ischaemia–reperfusion.8 These papers are hypothesis-generating: they list genes whose expression moved, not mechanisms that were confirmed.

Other research areas

Rodent neurochemistry work reports effects on dopaminergic and serotonergic activity.9 For a point-by-point look at how Semax compares with the tuftsin-derived peptide Selank, see Semax vs Selank.

Limits of the evidence

  • Most data are mRNA; protein-level and functional confirmation is thinner.
  • Most work is in rats and cell cultures, and much of it comes from a connected group of laboratories. Independent replication is limited.
  • Intact Semax and its PGP fragment overlap in effect, so attributing activity to the full molecule needs the comparison controls the authors used.
  • No single receptor target is established; one group reports specific binding in rat basal forebrain,5 but exposure-response relationships and receptor identity remain open.

Regulatory status

To our knowledge Semax is registered as a medicine in Russia and neighbouring countries and is not an authorised medicine in the EU or the United States. Regulatory positions change, so confirm current status with the relevant authority. Null Bio Lab supplies Semax solely as a reagent for in-vitro laboratory research under our terms.

Verifying a Semax batch

For a seven-residue peptide, a good report shows HPLC purity, a measured mass near the 814.36 [M+H]+ value above, measured quantity, and a batch number that matches the vial. Methionine can oxidise (+16 Da), so a small +16 signal is worth looking for. The full checklist is in how to read a peptide COA. The independent Janoshik report for the current batch is on the NB-Semax page and in the COA library.

Frequently asked questions

What is the Semax amino acid sequence?

Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP), a heptapeptide with a monoisotopic mass of 813.35 Da.

Is Semax the same as ACTH?

No. ACTH is a 39-residue hormone. Semax contains only a four-residue ACTH fragment, ACTH(4–7), joined to Pro-Gly-Pro.

What is the difference between “ACTH(4–10) analogue” and “ACTH(4–7)PGP”?

They describe the same molecule from two angles. Older papers compare it to ACTH(4–10); newer ones describe it as ACTH(4–7) plus PGP.

Is Semax approved by the FDA or EMA?

To our knowledge it is not an authorised medicine in the EU or US. Confirm current status with the regulator.

How can I check that a Semax batch is what it claims to be?

Compare the report’s HPLC purity, measured mass and batch number with the vial, and confirm the report on the testing laboratory’s own verification page. See the COA guide.

References

  1. 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. doi:10.1007/s10571-009-9432-0. PMID 19633950.
  2. Dolotov OV, et al. Semax, an analog of ACTH(4–10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Research. 2006. doi:10.1016/j.brainres.2006.07.108.
  3. Potaman VN, et al. Degradation of ACTH/MSH(4–10) and its synthetic analog semax by rat serum enzymes: an inhibitor study. Peptides. 1993. doi:10.1016/0196-9781(93)90137-6.
  4. Tabbì G, et al. Semax, an ACTH4-10 peptide analog with high affinity for copper(II) ion and protective ability against metal induced cell toxicity. Journal of Inorganic Biochemistry. 2015. doi:10.1016/j.jinorgbio.2014.09.008.
  5. Dolotov OV, et al. Semax, an analogue of adrenocorticotropin (4–10), binds specifically and increases levels of brain-derived neurotrophic factor in rat basal forebrain. Journal of Neurochemistry. 2006. doi:10.1111/j.1471-4159.2006.03658.x.
  6. Shadrina MI, et al. Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analog. Neuroscience Letters. 2001. doi:10.1016/s0304-3940(01)01994-2.
  7. 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;15:228. doi:10.1186/1471-2164-15-228.
  8. Filippenkov IB, 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. doi:10.3390/genes11060681.
  9. Eremin KO, et al. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochemical Research. 2005. doi:10.1007/s11064-005-8826-8.

Related reading

For newly published papers on this and other peptides, see the live feed on the Research Desk.