Semax vs Selank: Two Russian Heptapeptides Compared

Research-use-only context. This article summarizes published third-party scientific literature and laboratory practice. It is not medical advice, not a therapeutic or performance claim, and not a usage guide. US Prime Peptides products are supplied strictly for in vitro laboratory research and are not for human or veterinary use.

Semax and Selank are both seven-residue synthetic peptides developed at the Institute of Molecular Genetics in Moscow, and they are often sold side by side or together in one vial. This article compares them at the level of sequence origin, mass, proposed target class, the published cell and rodent literature, and what a certificate for each (or for the Semax/Selank blend) has to show.

The short answer: same tail, different heads

Semax is a fragment of adrenocorticotropic hormone (ACTH) joined to a Pro-Gly-Pro tail; Selank is a fragment of tuftsin, an immunoglobulin-derived tetrapeptide, joined to the same Pro-Gly-Pro tail. The two share their last three residues and nothing else. They differ in mass by about 60 Da, carry different net charges at neutral pH, and have been studied for different reasons: Semax mostly in neurotrophin-expression models, Selank mostly in gene-expression panels covering GABAergic neurotransmission and inflammation-related transcripts. Neither has a cloned receptor confirmed as its target.

Both are registered medicines in Russia and neither is an approved drug in the United States. A research vial of either compound is not the Russian product and is supplied only for in vitro work. The compound-level articles on Semax and Selank go deeper on each; this article is about the comparison.

Semax: an ACTH(4-7) fragment with a glyproline tail

Semax is the heptapeptide Met-Glu-His-Phe-Pro-Gly-Pro (molecular formula C₃₇H₅₁N₉O₁₀S, average mass about 813.9 Da). The first four residues are positions 4 through 7 of ACTH, the segment Met-Glu-His-Phe. The native ACTH(4-10) fragment continues Arg-Trp-Gly; Semax replaces that continuation with Pro-Gly-Pro. Because the melanocortin "message" motif is His-Phe-Arg-Trp, Semax lacks the Arg and Trp residues that melanocortin receptors recognize, which is why the originating group describes it as a non-corticotropic ACTH analog. A 2024 European Journal of Pharmacology paper by Inozemtseva and colleagues makes exactly this framing when it compares Semax with Melanotan II in a rat model, calling both "noncorticotropic synthetic analogs" of the ACTH(4-10) fragment.

The Pro-Gly-Pro tail is not decorative. A 2005 Pathophysiology paper by Ashmarin and colleagues describes the glyproline family (Pro-Gly-Pro-containing oligopeptides) as unusually resistant to proteolysis compared with most regulatory peptides, and a 2013 Doklady Biological Sciences report by Shevchenko and colleagues examined the stability of acetylated Semax in several biological media. The tail is the reason both Semax and Selank survive long enough in tissue preparations to be measured at all.

Semax also exists as an N-acetyl, C-amide variant (N-acetyl Semax amidate), which caps both termini. On a certificate this is a different molecule with a different expected mass (about 855 Da), and a vial labeled one way should not carry the other's mass-spectrometry line. The article on reading a peptide sequence explains how terminal caps change the mass you should expect.

Selank: a tuftsin fragment with the same tail

Selank is Thr-Lys-Pro-Arg-Pro-Gly-Pro (C₃₃H₅₇N₁₁O₉, average mass about 751.9 Da). The first four residues, Thr-Lys-Pro-Arg, are tuftsin, a tetrapeptide that sits in the Fc region of immunoglobulin G heavy chain and is released by enzymatic cleavage. The Pro-Gly-Pro tail was added for the same proteolytic-stability reason as in Semax. With a lysine and an arginine and no acidic residue, Selank carries a net positive charge at neutral pH, whereas Semax, with one glutamate and one histidine, is close to neutral. That charge difference matters for HPLC retention and for adsorption to plastic, which is why the two separate cleanly on a reverse-phase column even though they share three residues.

Selank has no identified receptor. The published hypotheses are indirect: modulation of GABA-A receptor function, which comes from pharmacological similarity rather than binding data, and inhibition of enkephalin-degrading enzymes. A 2002 Bulletin of Experimental Biology and Medicine paper by Sokolov and colleagues reported that Selank increased the half-life of leu-enkephalin in plasma from BALB/c mice, with strain-dependent differences against C57BL/6 mice. That is an enzyme-kinetics observation in a mouse plasma preparation, not a receptor identification.

Side-by-side comparison

The table shows why the two are grouped commercially despite being unrelated in origin: same length, same tail, same institute, same regulatory position, and a literature that comes mostly from overlapping author lists. It also shows the practical analytical difference: Semax has a methionine, so an oxidized (+16 Da) impurity peak is something to look for on its chromatogram; Selank has no oxidizable residue.

What the literature reports for Semax

The Semax literature is centered on neurotrophin expression in rat preparations. A 2001 Neuroscience Letters paper by Shadrina and colleagues reported that in glial cell cultures from newborn rat basal forebrain, BDNF mRNA rose about eight-fold and NGF mRNA about five-fold within 30 minutes of exposure to the peptide. A 2006 Brain Research paper by Dolotov and colleagues extended this to the rat hippocampus in vivo, reporting a 1.4-fold increase in BDNF protein, a 1.6-fold increase in trkB tyrosine phosphorylation, and increases in exon III BDNF and trkB mRNA. A 2007 Neuroscience Letters paper by Agapova and colleagues mapped neurotrophin gene expression across rat brain regions under the same peptide.

All of these are rodent or rat-cell findings from a single research lineage, and none identifies the molecular event upstream of the transcriptional change. No independent human mechanistic data exist in the English-language literature.

What the literature reports for Selank

The Selank literature leans on transcript panels. A 2016 Frontiers in Pharmacology paper by Volkova and colleagues measured 84 neurotransmission-related genes in rat frontal cortex and reported that 45 changed expression one hour after exposure to Selank, with a positive correlation to the changes produced by GABA itself. A 2017 Frontiers in Pharmacology paper by Filatova and colleagues ran a similar panel in IMR-32 neuroblastoma cells and found no expression changes from Selank alone, but reported that Selank nearly abolished the expression changes that GABA produced when the two were applied together. On the immune side, a 2011 Regulatory Peptides paper by Kolomin and colleagues profiled 84 inflammation-related genes in mouse spleen, and a 2014 Molecular Immunology follow-up by the same group tracked the time course of C3, Casp1, Il2rg and Xcr1 transcripts, finding that the Gly-Pro fragment reproduced several of the full peptide's effects.

The honest summary is that both compounds have a transcript-level literature in rodents and rat or human cell lines, almost entirely from one institute, with no receptor-binding assay and no independent replication from outside Russia for the core findings.

Why they share a bottle, and what the blend certificate must show

The two are blended because they come from the same program and are usually studied in the same model systems, not because any published paper tests a defined Semax-plus-Selank mixture. US Prime Peptides lists Semax 10 mg and Selank 10 mg as single-compound vials, and Semax/Selank 5 mg + 5 mg as a blend, each with a lot-matched certificate posted before purchase.

A blend certificate has to report two identities (mass spectrometry showing both the 813.9 Da and 751.9 Da species), two purity figures or one chromatogram with both main peaks resolved, and a per-component content line. Because Selank is more basic than Semax, the two elute at different retention times under a standard acetonitrile gradient, so co-elution is not the problem it can be for other pairs. The article on blends versus single compounds explains what a multi-peptide vial can and cannot tell a researcher.

Frequently Asked Questions

Are Semax and Selank the same peptide?

No. They share only the C-terminal Pro-Gly-Pro tail. Semax begins with the ACTH fragment Met-Glu-His-Phe and Selank begins with the tuftsin sequence Thr-Lys-Pro-Arg. They differ in mass (about 813.9 Da versus 751.9 Da), in net charge, and in the model systems used to study them.

Does Semax or Selank have a known receptor?

No receptor has been confirmed for either. Semax lacks the Arg-Trp residues of the melanocortin core motif, so it is not expected to bind melanocortin receptors the way ACTH does. Selank's proposed targets, GABA-A modulation and enkephalinase inhibition, are inferred from pharmacology and enzyme-kinetics data rather than binding studies.

Is Semax or Selank approved by the FDA?

Neither is an approved drug in the United States. Both are registered medicines in Russia. A research vial sold in the US is not the Russian product and is supplied only for in vitro laboratory use.

What should a Semax/Selank blend certificate show?

Two mass-spectrometry identities, one for each peptide, plus an HPLC chromatogram in which both main peaks are resolved, a purity figure for each component, and per-component net peptide content. The certificate should also state the Semax form, since the N-acetyl amidate variant has a different mass.

Citations

1. Shadrina MI, Dolotov OV, Grivennikov IA, et al. Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analog. Neurosci Lett. 2001;308(2):115-118. PMID 11457573
2. 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. PMID 16996037
3. Agapova TY, Agniullin YV, Shadrina MI, et al. Neurotrophin gene expression in rat brain under the action of Semax, an analogue of ACTH 4-10. Neurosci Lett. 2007;417(2):201-205. PMID 17353092
4. Inozemtseva LS, Yatsenko KA, Glazova NY, 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;984:177068. PMID 39442746
5. Ashmarin IP, Samonina GE, Lyapina LA, et al. Natural and hybrid ("chimeric") stable regulatory glyproline peptides. Pathophysiology. 2005;11(4):179-185. PMID 15837162
6. Shevchenko KV, Nagaev IY, Andreeva LA, et al. Stability of Semax acetyl to proteolysis in various biological media. Dokl Biol Sci. 2013;449:110-112. PMID 23652441
7. Volkova A, Shadrina M, Kolomin T, et al. Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission. Front Pharmacol. 2016;7:31. PMID 26924987
8. Filatova E, Kasian A, Kolomin T, et al. GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells. Front Pharmacol. 2017;8:89. PMID 28293190
9. Kolomin T, Shadrina M, Andreeva L, et al. Expression of inflammation-related genes in mouse spleen under tuftsin analog Selank. Regul Pept. 2011;170(1-3):18-23. PMID 21609736
10. Kolomin T, Morozova M, Volkova A, et al. The temporary dynamics of inflammation-related genes expression under tuftsin analog Selank action. Mol Immunol. 2014;58(1):50-55. PMID 24291245
11. Sokolov OY, Meshavkin VK, Kost NV, et al. Effects of Selank on behavioral reactions and activities of plasma enkephalin-degrading enzymes in mice with different phenotypes of emotional and stress reactions. Bull Exp Biol Med. 2002;133(2):133-135. PMID 12432865

This article is for laboratory research reference only. US Prime Peptides products are supplied strictly for in vitro research. Not for human consumption.

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