Selank — identity, handling and published literature

Selank is a synthetic heptapeptide analogue of the endogenous tetrapeptide tuftsin, supplied as a sterile lyophilised powder for laboratory use.

Presentation and physical properties

Selank is the tuftsin sequence Thr-Lys-Pro-Arg extended at the C-terminus by the tripeptide Pro-Gly-Pro. Three of its seven residues are proline, and it contains no cysteine, methionine, tryptophan, tyrosine or phenylalanine. Both facts govern most of its handling and analytical behaviour.

Reconstitution arithmetic

Reconstitution is a dilution calculation and nothing more. The mass in the vial is fixed; the concentration that results is determined entirely by the volume of diluent added. The relationship is concentration = mass ÷ volume.

The table below works that arithmetic for a 10 mg vial. It states concentrations only. It does not describe, imply or recommend any target amount, and no figure in it should be read as one.

Molar figures are derived from the labelled gross mass and a relative molecular mass of 751.9. Because the label includes counter-ion and residual water, a molar concentration calculated this way is an upper bound on the true value. Where molarity is a controlled variable in an experiment, net peptide content should be established by amino acid analysis or nitrogen determination rather than assumed from the label.

Storage and stability

Lyophilised. The dry solid is the stable form. Stored below −20 °C, sealed, desiccated and protected from light, a lyophilised peptide of this type is stable over extended periods. Because the cake is hygroscopic, vials should be allowed to reach ambient temperature before the seal is broken; opening a cold vial condenses atmospheric moisture onto the solid and begins hydrolysis in place.

In solution. Stability falls sharply once water is present. Aqueous solutions are held refrigerated and used over short periods, or frozen in single-use aliquots. Repeated freeze-thaw cycling should be avoided by aliquoting at the point of reconstitution rather than by returning a stock vial to the freezer; each cycle concentrates solutes at the ice front and promotes aggregation and adsorptive loss. Reconstitute by directing the diluent down the vial wall and dissolving by gentle swirling. Vigorous shaking generates foam and an extended air-liquid interface, at which peptides denature and adsorb.

Degradation routes determined by the sequence. Selank is unusually free of the residues that drive the common peptide degradation pathways, and this is worth stating explicitly because it changes which stability-indicating tests are informative:

• No asparagine or glutamine, so the deamidation pathway that dominates the degradation profile of most peptides is absent.
• No aspartate, so there is no aspartimide formation and no acid-labile Asp-Pro bond.
• No cysteine, so there is no thiol oxidation, no disulfide scrambling and no requirement for a reducing agent in solution.
• No methionine or tryptophan, so the classical oxidation markers used as stability indicators for other peptides do not apply here.

What remains are backbone hydrolysis, oxidation of the arginine guanidinium under metal-catalysed conditions, and reactions of the lysine ε-amine — which is nucleophilic and will react with reducing sugars and with activated carbonyl species should either be present in a formulation or a buffer. Trace metal contamination is therefore worth excluding from diluents, and chelation is a reasonable precaution in long-lived solutions.

The three proline residues confer relative resistance to proteolysis, which is the stated design rationale for the Pro-Gly-Pro extension on the parent tuftsin sequence. This is enzymatic resistance in a biological matrix and should not be read as chemical shelf stability, which is a separate property. Zolotarev and colleagues used uniformly tritium-labelled peptide to follow the biodegradation of Selank in blood plasma and reported the pentapeptide TKPRP, the tripeptide TKP and the dipeptides RP and GP as the major products, indicating sequential loss of dipeptide units from the C-terminal end [2].

Analytical identity

Reversed-phase HPLC. Selank is small, highly polar and doubly basic, so it is poorly retained on C18 under conventional conditions and elutes early, close to the void. Ion-pairing with trifluoroacetic acid at around 0.1 per cent in both mobile phases is normally required to obtain usable retention and peak shape. Hydrophilic interaction chromatography provides a genuinely orthogonal separation and is a better second method than a second reversed-phase gradient, which will tend to co-elute the same impurities.

Detection wavelength. Because the sequence contains no tryptophan, tyrosine or phenylalanine, there is effectively no absorbance at 280 nm. Detection must be at the peptide bond, near 214 nm. A method transferred from an aromatic-containing peptide without changing the wavelength will appear to show a clean or absent sample.

Proline isomerism. With three prolines, slow cis-trans isomerisation about the Xaa-Pro bonds can produce broadened, shouldered or apparently split peaks that are conformational rather than chemical. Raising the column temperature accelerates interconversion and typically sharpens the peak. A shoulder that collapses on heating is an isomer, not an impurity, and misreading it as one is a common error on proline-rich sequences.

Mass spectrometry. Expected masses for C₃₃H₅₇N₁₁O₉:

Three basic sites mean that doubly and triply charged ions are readily formed under electrospray conditions, and the doubly charged ion is often the base peak. Confirmation of identity requires sequence-informative fragmentation rather than intact mass alone, since intact mass cannot distinguish a sequence from its permutations. Vanhee and colleagues reported an LC-MS/MS method covering Selank among ten research peptides then offered for sale online, developed after two seized preparations were found to contain Selank and Semax, and constructed to comply with the European Official Medicines Control Laboratory network recommendation on interpreting mass-spectrometric screening results for unknown peptides [17].

What area-percent purity measures. An area-percent figure from RP-HPLC is the integrated area of the main peak expressed as a proportion of the total integrated area at one detection wavelength, under one set of chromatographic conditions. It is a useful and conventional measure, and it is routinely over-read.

It does not measure any of the following: the identity of the main peak; net peptide content, since counter-ion, residual water and residual solvents carry no chromophore at 214 nm and are invisible to the method; the presence of species that co-elute with the main peak; the presence of species that do not elute at all under the gradient used; endotoxin; bioburden; elemental impurities; or the conformational state of the material. A sample can return a high area-percent figure and still be substantially salt and water by mass. Mass balance requires an orthogonal quantitative method, and identity requires mass spectrometry. No pharmacopoeial monograph for Selank exists in the British Pharmacopoeia, the European Pharmacopoeia or the United States Pharmacopeia, so there is no compendial standard against which a certificate of analysis can be judged, and acceptance criteria are set by each supplier for itself.

What the published literature investigated

The material below reports what individual studies examined and what they stated they found. It is a record of a literature, not a characterisation of the substance, and nothing in it establishes any effect in humans.

In vitro

Zozulya and colleagues reported in 2001 that Selank inhibited the enzymatic hydrolysis of enkephalin in human plasma in a concentration-dependent manner, giving an IC₅₀ of 15 µM and describing the peptide as more potent in that assay than the peptidase inhibitors bacitracin and puromycin [1].

Filatova and colleagues examined the expression of genes associated with GABAergic neurotransmission in the IMR-32 human neuroblastoma line following exposure to GABA, Selank or olanzapine, and reported changes in expression across the panel [12]. Vyunova and colleagues used radioligand binding on isolated brain cell plasma membranes and reported that Selank altered [³H]GABA binding in a manner the authors interpreted as positive allosteric modulation, further reporting that its joint action with certain benzodiazepines was not simply additive [15].

Povarov and colleagues recorded spontaneous synaptic activity in rat hippocampal CA1 neurons under Selank and reported changes in that activity [13]. Kobylyanskii and colleagues screened several biologically active peptides including Selank for toxicity in a mouse embryonic stem cell model [14].

Rodent and other animal models

Volkova and colleagues assayed 84 neurotransmission-related genes in rat frontal cortex at one and three hours after administration of Selank or GABA, reporting significant expression changes in 45 genes at one hour and 22 at three hours, together with a positive correlation between the changes produced by the two compounds; the authors proposed allosteric modulation of the GABAergic system as one possible mechanism [10].

Inozemtseva and colleagues reported regulation of BDNF expression in the rat hippocampus [5]. Kolik and colleagues reported that Selank altered BDNF content in the hippocampus and prefrontal cortex of rats in a model of ethanol-induced memory impairment [16].

Kasian and colleagues assessed Selank and diazepam, separately and together, in rats under unpredictable chronic mild stress using the elevated plus maze, reporting that individual administration of Selank was the more effective of the single agents at reducing the elevated anxiety indicators induced by the test-substance course, while the diazepam-plus-Selank combination was the more effective under chronic stress conditions [11].

Kolomin and colleagues examined inflammation-related gene expression in mouse spleen under Selank [6] and subsequently characterised the time course of those expression changes [7]. Konstantinopolsky and colleagues reported attenuation of aversive signs of morphine withdrawal in rats [19].

Human

The human literature is small, is almost entirely Russian-language, and originates from a limited number of connected research groups.

Zozulya and colleagues reported a randomised comparative study of 62 patients with generalised anxiety disorder and neurasthenia, in which 30 received Selank and 32 received medazepam, assessed on the Hamilton, Zung and CGI scales with serum enkephalin activity measured alongside. The authors reported that the anxiolytic ratings for the two agents were similar, and that Selank additionally showed antiasthenic and psychostimulant effects on their measures [3].

Medvedev and colleagues reported a comparative study of Selank against phenazepam in 60 patients with phobic-anxiety and somatoform disorders classified under ICD-10 [8], and a subsequent randomised study on the same class of disorders [9].

Uchakina and colleagues reported cytokine measurements in patients with anxiety-asthenic disorders, describing changes in the Th1/Th2 balance in serum and effects on IL-6 in peripheral blood cell culture [4].

Reviews

Vyunova and colleagues reviewed the molecular aspects of Selank alongside their own binding data [15]. Doyno and White reviewed GABA receptor-active sedative-hypnotic agents, covering Selank among them, and characterised it as a poorly studied Russian drug being sold to consumers in the United States as a dietary supplement [18].

Evidence gaps and limitations

This section is the most important on the page. What follows is stated without qualification because the absences are the substantive fact about this compound.

There is no registered interventional clinical trial of Selank. A search of ClinicalTrials.gov by intervention returns no Selank study. Every human report cited above predates or sits outside the international trial registration system, so none carries a pre-registered protocol, a pre-specified primary endpoint or a public statistical analysis plan. Outcome-reporting bias cannot be excluded in any of them because there is no registered protocol against which the published outcomes could be checked.

The human evidence base is two small comparative studies and a cytokine study. The largest is 62 participants [3]; the next is 60 [8]. Studies of this size cannot characterise anything but common effects, and they cannot detect uncommon harms at all. None has been replicated by an independent group outside Russia. None has been published in English in full. Several share authors with one another and with the institute that developed the compound, and the published records do not describe independent adjudication or blinded outcome assessment in terms that can be verified from the abstracts.

No Western regulator has assessed it. There is no MHRA, EMA or FDA assessment report, which means no regulatory body outside the Russian Federation has examined the underlying trial data, the manufacturing controls or the safety database. The absence of a negative finding here is not a positive one; the data have simply never been submitted for that kind of scrutiny.

There is no published long-term safety data. The public literature contains no carcinogenicity study, no reproductive or developmental toxicology study, no genotoxicity battery and no chronic-exposure safety data in humans. The in vitro toxicity work that exists is a stem-cell screening model [14], which is a hazard-identification tool and not a substitute for any of the above.

Human pharmacokinetics are not established in the published literature. The biodegradation and distribution work available is in plasma and in rodents [2]. Absorption, systemic exposure, distribution, elimination and the pharmacological status of the degradation fragments in humans are not characterised in the accessible record.

The mechanism is proposed rather than settled. Two mechanistic accounts appear in the literature — inhibition of enkephalin-degrading enzymes [1] and allosteric modulation of GABAergic signalling [10][15] — and neither has been established as the operative one. Gene expression changes and radioligand binding shifts are observations at the level of a molecular assay; the step from those observations to any effect in a whole organism is not made by the studies that report them.

Material of unverified provenance is documented in circulation. Vanhee and colleagues encountered Selank in seized preparations and noted that peptides of this class are freely available online as lyophilised powder and in nasal sprays, which was their stated reason for developing a confirmatory method [17]. Nothing in the published record establishes the composition, purity or identity of material obtained outside a documented supply chain.

Nothing above establishes safety or efficacy for use in humans. Selank is a laboratory chemical. The literature summarised on this page describes experiments; it does not describe an authorised use.

Regulatory and standards position

Anti-doping. Selank is not named anywhere on the WADA Prohibited List. Its position is nevertheless not straightforwardly clear, and the reason is worth setting out rather than glossing. Section S0 of the List prohibits at all times any pharmacological substance not addressed by a later section and with no current approval by any governmental regulatory health authority for human therapeutic use. Selank holds a Russian registration, and the Russian medicines regulator is a governmental regulatory health authority, so on the literal wording S0 is arguable in both directions. No published decision resolves the point. An athlete subject to testing should obtain a determination from their national anti-doping organisation or international federation rather than infer permission from the absence of the name.

Laboratory handling and safety

No occupational exposure limit has been established for Selank and no comprehensive toxicological dossier exists. It should be handled as a biologically active substance of incompletely characterised hazard, which means the controls below are a floor rather than a considered maximum.

• Personal protective equipment. Nitrile gloves, safety spectacles and a laboratory coat as a minimum. Handle the dry lyophilisate in a containment device or a ducted enclosure: freeze-dried cake is light, holds a static charge and aerosolises readily when a vial is opened or a spatula is introduced.
• Weighing and transfer. Equilibrate vials to ambient temperature before opening. Weigh on an antistatic balance where available. Avoid generating dust; a fine peptide powder that becomes airborne is both an inhalation exposure and a cross-contamination route into neighbouring work.
• Spills. Do not dry-sweep or use compressed air. Dampen the spill with water to suppress dust, collect with absorbent material, and decontaminate the surface with 70 per cent ethanol or a dilute alkaline detergent. Dispose of the absorbent as chemical waste.
• Disposal. Peptide solutions, unused solid and contaminated consumables go to chemical waste in accordance with local rules and the site waste licence. Needles and glass go directly to a sharps container. Do not discharge peptide solutions to drain as a matter of routine.
• Hygiene. No eating, drinking or cosmetic use in the handling area. Wash hands on leaving it, including after glove removal.
• Record-keeping. Maintain a record for each vial covering supplier, lot or batch number, date of receipt, storage location and temperature, date of reconstitution, identity and volume of diluent, resulting concentration, number and volume of aliquots, and every freeze-thaw cycle applied. Retain the supplier certificate of analysis together with any in-house chromatographic or mass-spectrometric traces. Assign an in-house expiry to the reconstituted material and label every aliquot with compound, concentration, date and operator. Unlabelled solutions in a freezer are the commonest single cause of irreproducible peptide work.

References

1. Zozulya AA, Kost NV, Sokolov OYu, Gabaeva MV, Grivennikov IA, Andreeva LN, Zolotarev YA, Ivanov SV, Andryushchenko AV, Myasoedov NF, Smulevich AB. The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity. Bulletin of Experimental Biology and Medicine. 2001;131(4):315–317. Model: in vitro, human plasma. PMID 11550013
2. Zolotarev IuA, Dadaian AK, Dolotov OV, Kozik VS, Kost NV, Sokolov OIu, Dorokhova EM, Meshavkin VK, Inozemtseva LS, Gabaeva MV, Andreeva LA, Alfeeva LIu, Pavlov TS, Badmaeva KE, Badmaeva SE, Bakaeva ZV, Kopylova GN, Samonina GE, Vas’kovskii BV, Grivennikov IA, Zozulia AA, Miasoedov NF. Evenly tritium-labeled peptides and their in vivo and in vitro biodegradation. Bioorganicheskaia Khimiia. 2006;32(2):183–191. Russian. Model: in vitro plasma and rodent. PMID 16637290
3. Zozulia AA, Neznamov GG, Siuniakov TS, Kost NV, Gabaeva MV, Sokolov OIu, Serebriakova EV, Siranchieva OA, Andriushenko AV, Telesheva ES, Siuniakov SA, Smulevich AB, Miasoedov NF, Seredenin SB. Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2008;108(4):38–48. Russian. Model: human, randomised controlled trial, 62 participants. PMID 18454096
4. Uchakina ON, Uchakin PN, Miasoedov NF, Andreeva LA, Shcherbenko VE, Mezentseva MV, Gabaeva MV, Sokolov OIu, Zozulia AA, Ershov FI. Immunomodulatory effects of selank in patients with anxiety-asthenic disorders. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2008;108(5):71–75. Russian. Model: human and in vitro. PMID 18577961
5. Inozemtseva LS, Karpenko EA, Dolotov OV, Levitskaya NG, Kamensky AA, Andreeva LA, Grivennikov IA. Intranasal administration of the peptide Selank regulates BDNF expression in the rat hippocampus in vivo. Doklady Biological Sciences. 2008;421:241–243. Model: rodent. PMID 18841804
6. Kolomin T, Shadrina M, Andreeva L, Slominsky P, Limborska S, Myasoedov N. Expression of inflammation-related genes in mouse spleen under tuftsin analog Selank. Regulatory Peptides. 2011;170(1–3):18–23. Model: rodent. PMID 21609736
7. Kolomin T, Morozova M, Volkova A, Shadrina M, Andreeva L, Slominsky P, Limborska S, Myasoedov N. The temporary dynamics of inflammation-related genes expression under tuftsin analog Selank action. Molecular Immunology. 2014;58(1):50–55. Model: rodent. PMID 24291245
8. Medvedev VE, Tereshchenko ON, Israelian AIu, Chobanu IK, Kost NV, Sokolov OIu, Miasoedov NF. A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2014;114(7):17–22. Russian. Model: human, clinical trial, 60 participants. PMID 25176261
9. Medvedev VE, Tereshchenko ON, Kost NV, Ter-Israelyan AYu, Gushanskaya EV, Chobanu IK, Sokolov OYu, Myasoedov NF. Optimization of the treatment of anxiety disorders with selank. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2015;115(6):33–40. Russian. Model: human, randomised controlled trial. PMID 26356395
10. Volkova A, Shadrina M, Kolomin T, Andreeva L, Limborska S, Myasoedov N, Slominsky P. Selank administration affects the expression of some genes involved in GABAergic neurotransmission. Frontiers in Pharmacology. 2016;7:31. Model: rodent. PMID 26924987
11. Kasian A, Kolomin T, Andreeva L, Bondarenko E, Myasoedov N, Slominsky P, Shadrina M. Peptide Selank enhances the effect of diazepam in reducing anxiety in unpredictable chronic mild stress conditions in rats. Behavioural Neurology. 2017;2017:5091027. Model: rodent. PMID 28280289
12. Filatova E, Kasian A, Kolomin T, Rybalkina E, Alieva A, Andreeva L, Limborska S, Myasoedov N, Pavlova G, Slominsky P, Shadrina M. GABA, Selank, and olanzapine affect the expression of genes involved in GABAergic neurotransmission in IMR-32 cells. Frontiers in Pharmacology. 2017;8:89. Model: in vitro. PMID 28293190
13. Povarov IS, Kondratenko RV, Derevyagin VI, Myasoedov NF, Skrebitsky VG. Effect of Selank on spontaneous synaptic activity of rat hippocampal CA1 neurons. Bulletin of Experimental Biology and Medicine. 2017;162(5):640–642. Model: in vitro electrophysiology. PMID 28361410
14. Kobylyanskii AG, Zolotarev YuA, Andreeva LA, Grivennikov IA, Myasoedov NF. Studying the toxic effects of some biologically active peptides on the model of mouse embryonic stem cells. Bulletin of Experimental Biology and Medicine. 2017;163(6):731–736. Model: in vitro. PMID 29063333
15. Vyunova TV, Andreeva L, Shevchenko K, Myasoedov N. Peptide-based anxiolytics: the molecular aspects of heptapeptide Selank biological activity. Protein and Peptide Letters. 2018;25(10):914–923. Model: in vitro radioligand binding with review. PMID 30255741
16. Kolik LG, Nadorova AV, Antipova TA, Kruglov SV, Kudrin VS, Durnev AD. Selank, peptide analogue of tuftsin, protects against ethanol-induced memory impairment by regulating of BDNF content in the hippocampus and prefrontal cortex in rats. Bulletin of Experimental Biology and Medicine. 2019;167(5):641–644. Model: rodent. PMID 31625062
17. Vanhee C, Francotte A, Janvier S, Deconinck E. 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 Testing and Analysis. 2020;12(3):371–381. Model: analytical chemistry, LC-MS/MS method development. PMID 31667971
18. Doyno CR, White CM. Sedative-hypnotic agents that impact gamma-aminobutyric acid receptors: focus on flunitrazepam, gamma-hydroxybutyric acid, phenibut, and Selank. Journal of Clinical Pharmacology. 2021;61(Suppl 2):S114–S128. Model: review. PMID 34396551
19. Konstantinopolsky MA, Chernyakova IV, Kolik LG. Selank, a peptide analog of tuftsin, attenuates aversive signs of morphine withdrawal in rats. Bulletin of Experimental Biology and Medicine. 2022;173(6):730–733. Model: rodent. PMID 36322304

Research use only

Selank is supplied strictly as a laboratory chemical for research use only. It is not a medicine, it is not a supplement, and it is not authorised for human or veterinary use in the United Kingdom. It must not be administered to humans or to animals, and it must not be used in any diagnostic, therapeutic or food application.

Nothing on this page is a statement that Selank treats, prevents or otherwise affects any condition, and nothing here constitutes medical advice or guidance on use. The literature summarised above is reported as a record of what published studies examined and stated. Purchasers are responsible for ensuring that their intended work is lawful, that it is conducted by suitably qualified persons in an appropriately equipped facility, and that it holds any institutional or ethical approval required.