Semax vs Selank: two Pro-Gly-Pro heptapeptides compared

The short version

Semax and Selank are sister compounds. Both were developed at the Institute of Molecular Genetics of the Russian Academy of Sciences, both are seven residues long, and both were made by the same trick: take a short natural peptide fragment that is destroyed within seconds by peptidases, and add a C-terminal Pro-Gly-Pro that protects it and prolongs its action [1]. They differ in the fragment they start from. Semax begins with ACTH(4–7), a piece of adrenocorticotropic hormone with no effect on the adrenal gland, and has been studied for effects on attention, memory and neuronal survival. Selank begins with tuftsin, an immunomodulatory fragment of immunoglobulin G, and has been studied for anxiety-related behaviour and immune effects. Both are registered as medicines in Russia; neither is licensed in the UK, the EU or the United States.

Both are supplied by BuyUK Peptides as research chemicals for in-vitro laboratory use only.

Structure

The chemistry explains most of the practical differences. Semax carries an N-terminal methionine, which oxidises in solution, and an aromatic phenylalanine. Selank has no methionine and no aromatic residue, carries two basic side chains, and is unusually stable for a short peptide.

What the literature reports for Semax

The best-characterised finding is on neurotrophins: Dolotov and colleagues reported that Semax increased the expression of brain-derived neurotrophic factor and its receptor TrkB in the rat hippocampus [2]. Transcriptome studies in a rat model of cerebral ischaemia reported changes in large sets of immune, vascular and neurotransmission genes [3]. An early small human study reported effects on attention and memory [4], and the compound's Russian registration rests on a broader clinical literature published in Russian [5]. No single receptor has been identified.

What the literature reports for Selank

The recurrent findings are anxiolytic-like effects in standard rodent tests [6], changes in the expression of genes involved in GABAergic neurotransmission that overlap with those produced by a benzodiazepine reference compound [7], reported inhibition of enkephalin-degrading enzymes, and effects on cytokine expression inherited from the tuftsin parent [8]. Russian clinical trials in anxiety disorders supported its registration there [9]. As with Semax, there is no identified receptor.

The limits of the evidence

The two compounds share an evidence base with the same shape, and it is worth stating plainly. The animal literature is substantial and consistent within itself. The clinical literature comes almost entirely from Russian centres, much of it in Russian-language journals, and has not been replicated elsewhere or assessed by the MHRA, the EMA or the FDA. Mechanistic claims rest on gene-expression changes and enzyme effects rather than on a defined receptor. A laboratory working with either is working with a compound whose effects in defined in-vitro systems are still open questions, which is also what makes them interesting to study.

UK regulatory position

Neither is licensed in the UK or controlled under the Misuse of Drugs Act. Whether peptides of this kind fall within the Psychoactive Substances Act 2016 has not been tested; both are in any case supplied here as research chemicals for in-vitro laboratory use under the Terms of Sale, with no claim of any effect in people. Neither is named on the WADA Prohibited List. Our guide to the UK rules sets out the position.

Handling at the bench

Both dissolve at once in water or bacteriostatic water. Semax is the more delicate: its methionine oxidises in solution, so keep solutions cold, protected from light and with little air above them, and use within two to three weeks or aliquot and freeze. Selank is among the most stable peptides in the catalogue in solution, but as a strongly basic peptide it adsorbs to glass and to anionic surfaces at very low concentration, so use low-binding plastic for dilute working solutions. Choosing a reconstitution solvent covers both.

What to look for on the certificate

For both, RP-HPLC purity of 98 per cent or above at 214 or 220 nm. For Semax, the LC-MS identity line should show about 813.9 Da, usually as the singly charged ion at m/z 814.4; check for the methionine sulfoxide at plus 16 Da, which should be well under 1 per cent. For Selank, about 751.9 Da, usually seen as the doubly charged ion at m/z 376.7 because of its two basic residues; a certificate quoting purity at 280 nm is meaningless for it, since it has no aromatic residue. Net peptide content matters more for Selank than for most peptides, because its basic residues carry a heavy weight of counter-ion.

Which to choose

For research on neurotrophin expression, neuronal survival or the ACTH-fragment literature, Semax. For research on GABAergic gene expression, enkephalinase activity or the tuftsin immunological literature, Selank. Full accounts are in the monographs for Semax and Selank.

References

1. Kolomin T, Shadrina M, Slominsky P, Limborska S, Myasoedov N. A new generation of drugs: synthetic peptides based on natural regulatory peptides. Neuroscience & Medicine. 2013;4(4):223–252. doi:10.4236/nm.2013.44035.
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 Research. 2006;1117(1):54–60. doi:10.1016/j.brainres.2006.07.108.
3. Medvedeva EV, Dmitrieva VG, Limborska SA, et al. Semax, an analog of ACTH(4–7), regulates expression of immune response genes during ischemic brain injury in rats. Molecular Genetics and Genomics. 2017;292(3):635–653. doi:10.1007/s00438-017-1297-1.
4. Kaplan AY, Kochetova AG, Nezavibathko VN, Rjasina TV, Ashmarin IP. Synthetic ACTH analogue Semax displays nootropic-like activity in humans. Neuroscience Research Communications. 1996;19(2):115–123. doi:10.1002/(SICI)1520-6769(199609)19:2<115::AID-NRC171>3.0.CO;2-B.
5. Kaplan AY, Kochetova AG, Nezavibathko VN, Rjasina TV, Ashmarin IP. Synthetic ACTH analogue Semax displays nootropic-like activity in humans. Neuroscience Research Communications. 1996;19(2):115–123. doi:10.1002/(SICI)1520-6769(199609)19:2<115::AID-NRC171>3.0.CO;2-B.
6. Kozlovskii II, Danchev ND. The optimizing action of the synthetic peptide Selank on a conditioned active avoidance reflex in rats. Neuroscience and Behavioral Physiology. 2003;33(7):639–643. doi:10.1023/A:1024444321191.
7. Volkova A, Shadrina M, Kolomin T, et al. Selank administration affects the expression of some genes involved in GABAergic neurotransmission. Frontiers in Pharmacology. 2016;7:31. doi:10.3389/fphar.2016.00031.
8. Vyunova TV, Andreeva L, Shevchenko K, Myasoedov N. Peptide-based anxiolytics: the molecular aspects of heptapeptide Selank biological activity. Protein & Peptide Letters. 2018;25(10):924–929. doi:10.2174/0929866525666180925144642.
9. Zozulya AA, Neznamov GG, Syunyakov TS, et al. Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the treatment of generalized anxiety disorders and neurasthenia. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2008;108(4):38–48. PMID 18454096.

This monograph summarises the published literature for laboratory researchers. It is not medical advice, and nothing on this site is for human or veterinary use.