Selank: The Tuftsin Analog in the Research Literature

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.

This article surveys the published literature on Selank, a synthetic heptapeptide built on the immune tetrapeptide tuftsin, sorted by what each study measured and in which system: enzyme assays in human plasma, radioligand and gene-expression work on the GABA system, cytokine-gene profiling in mouse spleen, rodent behavioral models, and the Russian clinical record. It also explains how Selank differs chemically from Semax and states its regulatory position in the United States.

Selank is tuftsin with a Pro-Gly-Pro tail

Selank is the heptapeptide Thr-Lys-Pro-Arg-Pro-Gly-Pro (TKPRPGP), molecular formula C33H57N11O9, molecular weight about 751.9 daltons, PubChem CID 11765600, CAS 129954-34-3. The first four residues are tuftsin, a natural fragment of the immunoglobulin G heavy chain released by splenic enzymes; the C-terminal Pro-Gly-Pro is the same glyproline cap used on Semax, added to slow enzymatic breakdown. The peptide was developed jointly by the Institute of Molecular Genetics of the Russian Academy of Sciences and the Zakusov Institute of Pharmacology in Moscow, and it appears in the early literature under the development code TP-7.

Chemically, Selank is a basic, highly water-soluble peptide. Lysine and arginine carry positive charges at neutral pH, there is no methionine, cysteine or tryptophan, so oxidation in storage is not the main stability concern, and the three prolines give the backbone a rigid, kinked shape. The dominant breakdown route was mapped by Zolotarev and colleagues in a 2006 Bioorganicheskaia Khimiia paper using evenly tritium-labeled peptide: in blood plasma the main products were the pentapeptide Thr-Lys-Pro-Arg-Pro, the tripeptide Thr-Lys-Pro, and the dipeptides Arg-Pro and Gly-Pro. Those fragments matter because later gene-expression papers tested them alongside the parent and found that the dipeptide Gly-Pro reproduced several of its effects.

Selank is not an approved drug in the United States. It was registered as a medicinal product in the Russian Federation in 2009 in the anxiolytic class, which is why most of its human-use literature is in Russian-language journals. A 2021 review in the Journal of Clinical Pharmacology by Doyno and White described Selank and phenibut as poorly studied Russian drugs with GABA-related mechanisms that are nonetheless sold to US consumers as supplements, and called for abuse-potential evaluation before public access. A research vial is a laboratory chemical documented by a lot certificate. The Selank 10 mg listing shows that certificate format, and the Semax / Selank 5 mg / 5 mg blend listing shows how a two-component lot reports each peptide's identity and content separately.

Enkephalin-degrading enzymes: the first proposed mechanism

The earliest mechanistic hypothesis is enzyme inhibition. Zozulya and colleagues (2001, Bulletin of Experimental Biology and Medicine) reported that Selank inhibited enzymatic hydrolysis of leucine-enkephalin in human plasma with a half-maximal inhibitory concentration of about 15 micromolar, and that it was more potent in that assay than the peptidase inhibitors bacitracin and puromycin. The same group, in a 2001 Bioorganicheskaia Khimiia paper by Kost and colleagues, reported that both Semax and Selank inhibited enkephalin-degrading enzymes from human serum. Sokolov and colleagues (2002) extended the plasma assay to mice selected for different emotional reactivity phenotypes.

These are in vitro enzyme assays with a defined readout, which makes them among the cleaner data points in the Selank literature. What they do not establish is which enzyme is inhibited (the assays measure total enkephalin hydrolysis), whether the 15 micromolar potency is reached in any tissue, or whether the effect persists once the parent peptide has been cleaved to Thr-Lys-Pro and Gly-Pro. The 2006 Zolotarev paper is the right companion read for that last question.

The GABA system: radioligand, slice, and gene-expression studies

The second mechanism in the literature is allosteric modulation of GABA-A receptors. Vyunova and colleagues (2018, Protein and Peptide Letters) used radioligand binding on isolated brain-cell plasma membranes and reported that Selank increased tritiated-GABA binding in a concentration-dependent manner, that its combination with diazepam or olanzapine produced non-additive binding changes, and that the peptide's site appeared distinct from, though possibly overlapping, the benzodiazepine site. Povarov and colleagues (2017, Bulletin of Experimental Biology and Medicine) recorded rat hippocampal CA1 pyramidal neurons in slices and reported larger and more frequent spontaneous inhibitory postsynaptic currents across 1 to 8 micromolar, with no clear concentration dependence in that range and, in some cells, a transient decrease first.

Gene-expression work gives a more mixed picture. Volkova and colleagues (2016, Frontiers in Pharmacology) profiled 84 neurotransmission genes in rat frontal cortex and reported 45 changed at one hour and 22 at three hours, with a positive correlation between the Selank and GABA expression patterns at one hour. But Filatova and colleagues (2017, same journal) ran the same 84-gene panel in cultured human IMR-32 neuroblastoma cells and found no change in any transcript from Selank alone; the peptide did blunt the expression changes caused by GABA when the two were combined, and it increased the number of genes altered by olanzapine. The honest reading is that the GABAergic effect is detectable in rat tissue and in membrane binding, but not as a direct transcriptional effect in a human cell line. Kasian and colleagues (2017, Behavioural Neurology) added a rat elevated-plus-maze study of Selank with and without diazepam under unpredictable chronic mild stress, measuring anxiety indices before and after the stress protocol.

Cytokine and chemokine genes in mouse spleen

Because the parent tetrapeptide is an immune fragment, a line of work from the Institute of Molecular Genetics profiled inflammation genes. Kolomin and colleagues (2011, Regulatory Peptides) measured 84 inflammation-related transcripts in mouse spleen at 6 and 24 hours and reported 34 significantly changed, with the transcriptional repressor Bcl6 and several of its targets and corepressors moving in response to Selank and to each of its fragments. A 2014 Molecular Immunology paper from the same group tracked C3, Casp1, Il2rg and Xcr1 over short time points and reported a roughly three-fold fall in C3 mRNA within 30 minutes, a wave-like Casp1 pattern, early Il2rg changes, and a near-identical Xcr1 reduction at 90 minutes for the parent peptide and the dipeptide Gly-Pro. A 2011 Genetika paper compared chemokine and cytokine receptor expression for Selank and its fragments.

These are quantitative PCR studies in mouse tissue from a single laboratory. They establish that the peptide and its fragments change the abundance of specific immune transcripts over minutes to hours; they do not establish a receptor, a cell type, or a functional immune outcome. Readers comparing the immune angle of Selank with the ACTH-fragment angle of Semax can find the side-by-side in Semax vs Selank.

Rodent behavior, BDNF, and the human record

The rodent behavioral literature is extensive and spans two decades. Kozlovskaya and colleagues (2003, Neuroscience and Behavioral Physiology) compared Selank with ten tuftsin-family peptides in rats and in C57BL/6 and BALB/c mice separated by emotional reactivity, scoring behavior in a conflict-stress paradigm. Inozemtseva and colleagues (2008, Doklady Biological Sciences) reported BDNF expression changes in rat hippocampus, and Kolik and colleagues (2019, Bulletin of Experimental Biology and Medicine) measured BDNF content in hippocampus and prefrontal cortex in an ethanol memory-impairment model. Papers from the Zakusov Institute between 2014 and 2022 report Selank in rat models of alcohol and morphine withdrawal, scoring withdrawal signs. A 2017 Doklady Biological Sciences paper by Slominsky and colleagues scored behavior of rats with 6-hydroxydopamine lesions after Semax or Selank.

The human record exists because of the Russian registration. Zozulia and colleagues (2008, Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova) compared Selank with medazepam in 62 adults with generalized anxiety disorder or neurasthenia using the Hamilton, Zung and CGI scales, and also measured leucine-enkephalin half-life in serum. Medvedev and colleagues (2014, same journal) compared Selank with phenazepam in 60 adults with anxiety-phobic and somatoform diagnoses. Both are open comparative designs published in Russian; neither is a blinded, placebo-controlled trial of the type reviewed in a US or EU drug application, and neither has been replicated outside Russia.

How Selank differs from Semax, and what a certificate should show

Selank and Semax share only the Pro-Gly-Pro cap. Semax derives from ACTH(4-7) and is acidic-to-neutral with a metal-binding histidine; Selank derives from tuftsin and is basic, with lysine and arginine. The two have different proposed mechanisms (BDNF and melanocortin-related work for Semax; enkephalinase and GABA-A modulation for Selank) and different registered uses in Russia. They are frequently sold together, and because both are small and polar, a blend certificate must show two separate mass-spectrometry identities (about 751.9 and 813.9 daltons) and two HPLC content values, not a single purity number. The reasons are laid out in Reading a Blend Certificate.

For a single-compound lot, the identity line should show the protonated mass near 752.4, the HPLC purity should be reported at a stated wavelength (short proline-rich peptides are usually read at 214 or 220 nanometers because they lack aromatic residues), and the net peptide content should account for the counter-ion, which for a basic peptide with two cationic residues can be a meaningful share of the vial mass. The Selank liquid spray 5 mg listing documents the labeled mass for the solution format, where the certificate also reports the preservative and the per-bottle content. How counter-ions affect that figure is covered in Net Peptide Content vs Purity.

Frequently Asked Questions

What is Selank made from?

Selank is the heptapeptide Thr-Lys-Pro-Arg-Pro-Gly-Pro. Its first four residues are tuftsin, a natural immunoglobulin G fragment, and the last three are a Pro-Gly-Pro cap that slows enzymatic breakdown. It was developed at the Institute of Molecular Genetics and the Zakusov Institute of Pharmacology in Moscow.

Is Selank an approved drug in the United States?

No. Selank is not approved by the FDA. It was registered as a medicinal product in Russia in 2009, and a 2021 Journal of Clinical Pharmacology review flagged its sale to US consumers as a supplement as a regulatory gap. In the US it is sold strictly as a research chemical.

How does Selank interact with the GABA system in research?

Radioligand work (Vyunova 2018) reported increased tritiated-GABA binding on brain-cell membranes, and slice recordings (Povarov 2017) reported larger inhibitory postsynaptic currents in rat CA1 neurons. In cultured human IMR-32 cells, however, Selank alone changed none of 84 GABA-related transcripts, so the effect is not a direct transcriptional one.

What is the difference between Selank and Semax?

They share only the Pro-Gly-Pro tail. Semax is an ACTH(4-7) analog studied mainly for BDNF and transcriptome effects; Selank is a tuftsin analog studied for enkephalinase inhibition, GABA-A modulation and immune-gene expression. Their masses differ (about 752 vs 814 daltons), so a blend certificate must identify each separately.

Citations

1. Zozulya AA, Kost NV, Sokolov OY, et al. The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity. Bull Exp Biol Med. 2001;131:315-317. PMID 11550013
2. Kost NV, Sokolov OY, Gabaeva MV, et al. Semax and selank inhibit the enkephalin-degrading enzymes from human serum [in Russian]. Bioorg Khim. 2001;27:180-183. PMID 11443939
3. Sokolov OY, Kost NV, Andreeva LA, 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;133:133-135. PMID 12432865
4. Zolotarev YA, Dadayan AK, Dolotov OV, et al. Evenly tritium-labeled peptides and their in vivo and in vitro biodegradation [in Russian]. Bioorg Khim. 2006;32:183-191. PMID 16637290
5. Vyunova TV, Andreeva L, Shevchenko K, Myasoedov N. Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity. Protein Pept Lett. 2018;25:914-923. PMID 30255741
6. Povarov IS, Kondratenko RV, Derevyagin VI, Myasoedov NF, Skrebitsky VG. Effect of Selank on Spontaneous Synaptic Activity of Rat Hippocampal CA1 Neurons. Bull Exp Biol Med. 2017;162:640-642. PMID 28361410
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. Kasian A, Kolomin T, Andreeva L, et al. Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats. Behav Neurol. 2017;2017:5091027. PMID 28280289
10. Kolomin T, Shadrina M, Andreeva L, Slominsky P, Limborska S, Myasoedov N. Expression of inflammation-related genes in mouse spleen under tuftsin analog Selank. Regul Pept. 2011;170:18-23. PMID 21609736
11. Kolomin T, Morozova M, Volkova A, et al. The temporary dynamics of inflammation-related genes expression under tuftsin analog Selank action. Mol Immunol. 2014;58:50-55. PMID 24291245
12. Kolomin TA, Shadrina MI, Agapova TY, et al. Changes in expression of the genes for chemokines, cytokines, and their receptors in response to selank and its fragments [in Russian]. Genetika. 2011;47:711-714. PMID 21786679
13. Kozlovskaya MM, Kozlovskii II, Val'dman EA, Seredenin SB. Selank and short peptides of the tuftsin family in the regulation of adaptive behavior in stress. Neurosci Behav Physiol. 2003;33:853-860. PMID 14969422
14. Inozemtseva LS, Karpenko EA, Dolotov OV, et al. Intranasal administration of the peptide Selank regulates BDNF expression in the rat hippocampus in vivo. Dokl Biol Sci. 2008;421:241-243. PMID 18841804
15. Kolik LG, et al. Selank, Peptide Analogue of Tuftsin, Protects Against Ethanol-Induced Memory Impairment by Regulating of BDNF Content in the Hippocampus and Prefrontal Cortex in Rats. Bull Exp Biol Med. 2019;167:641-644. PMID 31625062
16. Slominsky PA, et al. Peptides semax and selank affect the behavior of rats with 6-OHDA induced PD-like parkinsonism. Dokl Biol Sci. 2017;474:106-109. PMID 28702721
17. Zozulia AA, Neznamov GG, Siuniakov TS, et al. Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108:38-48. PMID 18454096
18. Medvedev VE, Tereshchenko ON, Israelian AY, et al. A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 2014;114:17-22. PMID 25176261
19. Doyno CR, White CM. Sedative-Hypnotic Agents That Impact Gamma-Aminobutyric Acid Receptors: Focus on Flunitrazepam, Gamma-Hydroxybutyric Acid, Phenibut, and Selank. J Clin Pharmacol. 2021;61 Suppl 2:S114-S128. PMID 34396551

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