What Is Semax? The ACTH(4-7)-Pro-Gly-Pro Heptapeptide

Semax is a synthetic heptapeptide, Met-Glu-His-Phe-Pro-Gly-Pro. It joins the ACTH(4-7) fragment of adrenocorticotropic hormone to a Pro-Gly-Pro (PGP) tripeptide. It was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences, and most of its literature comes from Russian groups studying neurotrophin expression in rodent brain-injury models.

For laboratory research use only. The compounds discussed are not approved for human or veterinary use and are not drugs, foods or cosmetics. This article summarises published research and is not medical advice.

Key points

Sequence MEHFPGP; C₃₇H₅₁N₉O₁₀S, 813.9 g/mol.
ACTH(4-7) + PGP; often described as an ACTH(4-10) analogue.
Main research theme: BDNF/NGF and Trk receptor transcription after experimental ischemia.
Major breakdown products: HFPGP and PGP; inhibits plasma enkephalinase aminopeptidases.
Contains methionine and histidine: sensitive to oxidation and binds copper/zinc.

Quick facts

Property	Value
Sequence	Met-Glu-His-Phe-Pro-Gly-Pro
Formula / weight	C₃₇H₅₁N₉O₁₀S, 813.9 g/mol (PubChem CID 9811102)
Parent fragment	ACTH(4-7)
C-terminal extension	Pro-Gly-Pro
Common derivative	N-acetyl Semax (often amidated)
Status	Not approved in the US or EU

Our Semax research peptide is supplied in 5 mg and 10 mg vials with lot-level HPLC and MS data.

Neurotrophin research

The most cited mechanistic work concerns neurotrophins. In rats with permanent middle cerebral artery occlusion, Semax increased cortical transcription of Bdnf, TrkC and TrkA at 3 hours, Nt-3 and Ngf at 24 hours, and Ngf at 72 hours. PGP alone also activated neurotrophin and receptor transcription, with a partly overlapping profile (Dmitrieva et al., 2010). That paper describes Semax as used in Russia for acute stroke therapy, a regulatory status that does not extend to the US or EU.

Model	Finding	Study
Rat cerebral ischemia (pMCAO)	Increased neurotrophin and Trk receptor transcription	Dmitrieva et al., 2010
Rats after early-life fluvoxamine exposure	Attenuated behavioural and neurochemical alterations	Glazova et al., 2021
Female mice, spinal cord injury	Linked to Oprm1 (μ-opioid receptor gene) deubiquitination and functional recovery	Liu et al., 2025

How Semax is broken down

Using evenly tritium-labelled peptides, Zolotarev and colleagues showed that in the presence of nerve cells, Semax is degraded mainly to the pentapeptide HFPGP and the tripeptide PGP. In other words, cleavage proceeds from the N-terminus. The same work found that Semax strongly inhibits enkephalin-degrading enzymes in blood plasma, an effect attributed to its action on aminopeptidases (Zolotarev et al., 2006).

Fragment	Sequence	Note
Parent	MEHFPGP	813.9 g/mol
Major product	HFPGP	Loss of Met-Glu
Major product	PGP	Itself biologically active in rodent studies

N-terminal degradation is the rationale for N-acetylated Semax, which blocks the free amine; see N-acetyl Semax amidate explained.

Half-life

We did not find a peer-reviewed human pharmacokinetic study giving a half-life for Semax. The biodegradation data above describe rapid enzymatic processing, as expected for a short, unmodified linear peptide. Values quoted online without a citation should be treated with caution.

Metal binding

Semax’s histidine allows it to bind Cu(II) and Zn(II). Acetylating the N-terminus changes which copper complexes form at physiological pH and alters some biological properties in vitro (Magrì et al., 2016). In the lab this means metal contamination of buffers can matter more for Semax than for peptides without histidine.

Identity testing

Semax and Selank have been found together in seized preparations; a Belgian control laboratory developed an LC-MS/MS method to identify them reliably (Vanhee et al., 2020). On a COA, MS should match 813.9 g/mol; a +16 Da species indicates methionine oxidation.

Handling in the lab

Store powder at −20 °C, sealed and dark; solutions at 2–8 °C.
Minimise air and light to protect Met1 from oxidation.
Water-soluble; reconstitute with bacteriostatic or sterile water (method).
Use the peptide reconstitution calculator for concentrations.

Open questions

What is the human pharmacokinetic profile of Semax, including half-life, by different administration routes?
How much of Semax’s activity comes from its PGP and HFPGP fragments rather than the intact heptapeptide?
Have the neurotrophin findings been replicated by groups outside the original research network?

Related research

Frequently asked questions

What is Semax?

Semax is a synthetic heptapeptide, Met-Glu-His-Phe-Pro-Gly-Pro. It combines the ACTH(4-7) fragment of adrenocorticotropic hormone with a C-terminal Pro-Gly-Pro tripeptide. It was developed by researchers at the Russian Academy of Sciences.

What does Semax do in research models?

Rodent studies link Semax to increased transcription of neurotrophins (BDNF, NGF) and their Trk receptors, notably after experimental cerebral ischemia. Other studies have examined it in models of early-life stress and spinal cord injury.

How is Semax broken down?

In the presence of nerve cells, the main breakdown products are the pentapeptide His-Phe-Pro-Gly-Pro and the tripeptide Pro-Gly-Pro. Semax also inhibited enkephalin-degrading aminopeptidases in blood plasma.

What is the half-life of Semax?

We did not find a peer-reviewed human half-life value. Tritium-labelling studies describe rapid enzymatic cleavage from the N-terminus, consistent with a short circulating lifetime typical of small unmodified peptides.

Does Semax need to be refrigerated?

As research material, store the powder at −20 °C and solutions at 2–8 °C. Semax contains methionine, which oxidises in the presence of air and light.

References

Dmitrieva VG, et al. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. Cell Mol Neurobiol. 2010. PMID: 19633950 https://pubmed.ncbi.nlm.nih.gov/19633950/
Zolotarev IuA, et al. [Evenly tritium-labeled peptides and their in vivo and in vitro biodegradation]. Bioorg Khim. 2006. PMID: 16637290 https://pubmed.ncbi.nlm.nih.gov/16637290/
Magrì A, et al. Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties. J Inorg Biochem. 2016. PMID: 27586814 https://pubmed.ncbi.nlm.nih.gov/27586814/
Glazova NY, et al. Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats. Neuropeptides. 2021. PMID: 33418449 https://pubmed.ncbi.nlm.nih.gov/33418449/
Liu R, et al. Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice. Br J Pharmacol. 2025. PMID: 40692165 https://pubmed.ncbi.nlm.nih.gov/40692165/
Vanhee C, et al. The occurrence of putative cognitive enhancing research peptides in seized pharmaceutical preparations: An incentive for controlling agencies to prepare for future encounters of the kind. Drug Test Anal. 2020. PMID: 31667971 https://pubmed.ncbi.nlm.nih.gov/31667971/
PubChem Compound Summary for CID 9811102, Semax. National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/compound/9811102