Semax vs Selank: Structure and Research Compared

Semax and Selank are synthetic heptapeptides that are often mentioned together, and for a structural reason: both end in the same Pro-Gly-Pro tripeptide. The difference lies in the front half. Semax is built on a fragment of adrenocorticotropic hormone (ACTH), and Selank on tuftsin, an immunoglobulin-derived tetrapeptide. That difference largely explains why the two literatures have followed separate paths: neurotrophins for Semax, GABA and enkephalinase for Selank.

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

Same length (7 residues) and the same C-terminal Pro-Gly-Pro, but unrelated N-terminal “parent” sequences.
Semax research focuses on BDNF/NGF and Trk receptor transcription in rodent brain-injury models.
Selank research focuses on GABA receptor binding, GABA-related gene expression and enkephalin-degrading enzymes.
One fMRI study in 52 healthy volunteers compared both peptides directly.
Neither peptide is an approved medicine in the US or EU.

Side-by-side comparison

	Semax	Selank
Sequence	Met-Glu-His-Phe-Pro-Gly-Pro	Thr-Lys-Pro-Arg-Pro-Gly-Pro
Parent peptide	ACTH(4-7), a fragment of adrenocorticotropic hormone	Tuftsin (Thr-Lys-Pro-Arg), derived from immunoglobulin G
Shared motif	C-terminal Pro-Gly-Pro (PGP)
Molecular formula	C₃₇H₅₁N₉O₁₀S	C₃₃H₅₇N₁₁O₉
Molecular weight	813.9 g/mol	751.9 g/mol
Net character at neutral pH	Mixed: one acidic residue (Glu), one His	Basic: two strongly basic residues (Lys, Arg)
Main research themes	Neurotrophin expression, ischemia models, metal coordination	GABAergic signalling, enkephalinase inhibition, stress models
Common modified form	N-acetyl Semax (Ac-Semax), often as the amidate	N-acetyl Selank, often as the amidate

Material for laboratory work is available as Semax and Selank research peptides, each with lot-level HPLC and MS data.

Why both peptides end in Pro-Gly-Pro

Short regulatory peptides such as ACTH fragments and tuftsin are readily degraded by peptidases, and the proline-rich PGP extension is generally described as a stabilising modification. PGP is not just a spacer, though. Dmitrieva and colleagues tested Semax and PGP separately in rats with permanent middle cerebral artery occlusion and found that both increased transcription of neurotrophin genes in the cortex, with partly overlapping profiles (Dmitrieva et al., 2010). Researchers comparing the two heptapeptides therefore often include PGP alone as a control.

Semax: what has been studied

Semax combines ACTH(4-7) (Met-Glu-His-Phe) with PGP. The fragment lacks the corticotropic (adrenal-stimulating) role of full-length ACTH, and research has concentrated on the central nervous system.

Neurotrophins: in the rat ischemia model above, Semax increased transcription of Bdnf, TrkC and TrkA 3 hours after occlusion, and Nt-3 and Ngf at 24 hours (Dmitrieva et al., 2010).
Metal coordination: the His residue lets Semax bind Cu(II) and Zn(II). Acetylating the N-terminus (Ac-Semax) changes which copper complexes form at physiological pH, and with it some of the peptide’s biological properties in vitro (Magrì et al., 2016). This is one reason the N-acetyl form is treated as a distinct compound; see N-acetyl Semax amidate explained.

For a full profile of the peptide, see what is Semax?.

Selank: what has been studied

Selank extends tuftsin (Thr-Lys-Pro-Arg) with PGP and is described in the literature as a tuftsin analogue (Konstantinopolsky et al., 2022). Its research themes differ clearly from Semax:

GABA receptor binding: in radioligand assays on rat brain membranes, Selank behaved as a positive allosteric modulator of [³H]GABA binding. Its combined effect with benzodiazepines was not simply additive (Vyunova et al., 2018).
Gene expression: real-time PCR of 84 neurotransmission-related genes in rat frontal cortex showed changes in 45 genes one hour after administration of Selank or GABA, and in 22 genes after three hours. The changes produced by the two substances were positively correlated (Volkova et al., 2016).
Enkephalinase inhibition: in human plasma, Selank inhibited enkephalin-degrading peptidases, acting more specifically on carboxypeptidases and dipeptidyl carboxypeptidases than the reference inhibitor bestatin (Zolotarev et al., 2004).

See what is Selank? for the full compound profile, including the N-acetylated form.

Studies that compared the two directly

Direct comparisons are rare. In a resting-state functional MRI study, 52 healthy participants were scanned before and 5 and 20 minutes after receiving Semax, Selank or placebo. The authors reported between-group differences in connectivity between the right amygdala and a region spanning the fusiform, inferior and middle temporal and parahippocampal gyri, and described both shared and peptide-specific patterns (Panikratova et al., 2020). It is a single, small study published as a short communication, so it cannot settle how the two peptides differ in humans.

Identity testing: telling them apart in the lab

Because they have similar length and share three residues, Semax and Selank need a selective method for identity confirmation. A Belgian control laboratory that identified both peptides in seized preparations developed a combined LC-MS/MS method suitable for hydrophilic and more hydrophobic peptides (Vanhee et al., 2020). In routine quality control, the most reliable differentiator is mass: the roughly 62 Da difference between the two parent masses is easy to resolve by ESI-MS, while HPLC retention time confirms purity. Our guide to peptide purity testing explains how to read these results on a certificate of analysis.

Handling in the lab

Step	Semax	Selank
Supplied as	Lyophilized powder; the salt form (often acetate) is stated on the COA
Solubility	Water-soluble	Water-soluble; the basic residues aid dissolution
Oxidation-sensitive residue	Met (can oxidise to the sulfoxide, +16 Da by MS)	None
Long-term storage (powder)	−20 °C, sealed, protected from light
After reconstitution	2–8 °C; avoid repeated freeze–thaw; record the date

The methionine in Semax is the main practical difference: minimise headspace air and light exposure for both powder and solution. To calculate solution concentration, use the peptide reconstitution calculator and see how to reconstitute peptides.

Related research

Semax half-life: what has been measured
N-acetyl Selank amidate vs Selank
Adamax vs Semax

Frequently asked questions

What is the main difference between Semax and Selank?

They come from different parent peptides. Semax is built on the ACTH(4-7) fragment of adrenocorticotropic hormone; Selank is built on tuftsin, a tetrapeptide derived from immunoglobulin G. Both carry the same C-terminal Pro-Gly-Pro extension.

Are Semax and Selank the same length?

Yes. Both are heptapeptides (seven amino acids): Semax is Met-Glu-His-Phe-Pro-Gly-Pro and Selank is Thr-Lys-Pro-Arg-Pro-Gly-Pro. Their molecular weights are about 814 and 752 g/mol respectively.

What mechanisms have been studied for each peptide?

Semax research centres on neurotrophin expression (BDNF, NGF and their Trk receptors) in rodent ischemia models. Selank research centres on GABAergic signalling, including allosteric effects on GABA binding and changes in GABA-related gene expression, and on inhibition of enkephalin-degrading enzymes.

Have Semax and Selank been studied together?

Yes. A resting-state fMRI study in 52 healthy volunteers compared the two peptides with placebo and reported both shared and peptide-specific changes in connectivity between the right amygdala and the temporal cortex.

Are Semax and Selank approved medicines in the US or EU?

No. Most of the literature comes from Russian research groups. A 2020 analytical paper on seized preparations noted that, to the authors’ knowledge, neither peptide had completed clinical trials in the sense required for Western approval.

References

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/
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/
Vyunova TV, et al. Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity. Protein Pept Lett. 2018. PMID: 30255741 https://pubmed.ncbi.nlm.nih.gov/30255741/
Volkova A, et al. Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission. Front Pharmacol. 2016. PMID: 26924987 https://pubmed.ncbi.nlm.nih.gov/26924987/
Zolotarev IuA, et al. [Leu-enkephalin homogeneously labeled with tritium in studying the Selank inhibiting effect on the enkephalin-degrading enzymes of human plasma]. Bioorg Khim. 2004. PMID: 15344652 https://pubmed.ncbi.nlm.nih.gov/15344652/
Konstantinopolsky MA, et al. Selank, a Peptide Analog of Tuftsin, Attenuates Aversive Signs of Morphine Withdrawal in Rats. Bull Exp Biol Med. 2022. PMID: 36322304 https://pubmed.ncbi.nlm.nih.gov/36322304/
Panikratova YR, et al. Functional Connectomic Approach to Studying Selank and Semax Effects. Dokl Biol Sci. 2020. PMID: 32342318 https://pubmed.ncbi.nlm.nih.gov/32342318/
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
PubChem Compound Summary for CID 11765600, Selank. National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/compound/11765600