Selank: A Research Overview

Introduction

Selank is a synthetic heptapeptide with the amino acid sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. Developed at the Institute of Molecular Genetics of the Russian Academy of Sciences in Moscow, it was designed as a metabolically stabilized structural analog of tuftsin (Thr-Lys-Pro-Arg) — a naturally occurring tetrapeptide fragment of immunoglobulin G. Research spanning approximately three decades has characterized Selank across GABAergic, enkephalinergic, and neurotrophin-mediated pharmacological pathways in preclinical models, with clinical investigation conducted in Russia culminating in regulatory registration in 2009 [1,2].

Background

Tuftsin, first described by Najjar and Nishioka in 1970, is a naturally occurring immunomodulatory tetrapeptide generated by proteolytic cleavage from the heavy chain of IgG [3]. Although tuftsin exhibits immunostimulatory and neuromodulatory activity in preclinical models, its very rapid enzymatic degradation in plasma — with a reported half-life of seconds — constrained its translational utility [3]. Research programs at the Institute of Molecular Genetics initiated in the late 1980s and early 1990s sought to engineer a metabolically stable derivative that retained and extended tuftsin's pharmacological profile.

The approach was to append a Pro-Gly-Pro tripeptide sequence to tuftsin's C-terminus. This extension was reported to confer substantially greater resistance to plasma peptidases compared to the parent molecule while preserving immunomodulatory properties and introducing pronounced neurotropic activity not prominent in tuftsin itself [1,2]. Myasoedov and colleagues described the development of Selank as part of a program to generate synthetic regulatory peptide drugs for clinical application [1].

Chemistry and Structure

Selank is a linear heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. The molecular formula is C33H57N11O9 and the molecular weight is approximately 751.9 Da. All amino acid residues are in the L-configuration. The compound is synthesized by solid-phase peptide synthesis (SPPS).

The C-terminal Pro-Gly-Pro extension is the structural feature that distinguishes Selank from tuftsin and is understood to underpin the compound's enhanced metabolic stability: the proline residues flanking the glycine at positions five and seven are resistant to cleavage by many endopeptidases, a property characteristic of proline-rich sequences in bioactive peptides. A 2019 comparative analysis in Biology Bulletin evaluated the pharmacological contributions of individual Selank fragments — including the core tuftsin tetrapeptide and the Pro-Gly-Pro C-terminal sequence — providing structure-activity characterization of the intact heptapeptide [4].

A related compound, N-acetyl Selank amidate, incorporates N-terminal acetylation and C-terminal amidation to further resist exopeptidase cleavage. Published pharmacological data on the amidate form are at an earlier stage than those for Selank itself and are not the primary focus of this overview.

Pharmacological Classification

Selank is classified in the pharmacological literature as a synthetic neuropeptide with GABAergic modulatory and immunomodulatory activity. Research has characterized the compound's activity across three intersecting neuromodulatory mechanisms: modulation of GABAergic neurotransmission gene expression, inhibition of enkephalin-degrading enzymes, and regulation of brain-derived neurotrophic factor (BDNF) expression in preclinical models [5,6,7].

Importantly, Selank does not belong to the benzodiazepine, barbiturate, or azapirone chemical classes. Russian clinical pharmacology literature categorizes the compound under neuropeptide anxiolytics — a classification distinct from classical sedating anxiolytics — based on preclinical and clinical observations reporting an absence of sedative, muscle-relaxant, or anticonvulsant effects at pharmacologically active concentrations in animal models and clinical subjects [1,2]. The compound has also been characterized as an immunomodulator, owing to research demonstrating effects on cytokine gene expression and immune cell activity in both preclinical and clinical settings [8].

Regulatory Status

Selank received registration approval from the Russian Federation Ministry of Health in 2009, and has since been available by medical prescription in Russia as a 0.15% nasal drop solution indicated for generalized anxiety disorder and neurasthenic conditions [1,2]. The drug was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences and brought to registration through collaboration with Russian pharmaceutical entities.

Selank does not hold regulatory approval from the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA), or comparable regulatory bodies in other major jurisdictions. Outside Russia, the compound is not approved for any therapeutic indication and is not classified as a drug. Regulatory status varies by jurisdiction, and researchers working with this compound are responsible for confirming applicable local regulations.

Discovery History

The synthesis and initial biological evaluation of Selank were carried out in the late 1980s and early 1990s at the Institute of Molecular Genetics, principally by the group of Nikolay Myasoedov and Lyudmila Andreeva in the Department of Chemistry of Physiologically Active Compounds. Early preclinical work published in Russian-language pharmacological journals documented behavioral effects in animal models that distinguished the compound from both tuftsin and classical sedating anxiolytics.

Early English-language accounts appeared in Neuroscience and Behavioral Physiology in 2003, reporting effects in conditioned active avoidance and stress paradigms in rodents [9,10]. Preclinical characterization expanded through the 2000s and 2010s to encompass molecular investigations of GABAergic gene expression, enkephalinase activity, BDNF regulation, and hippocampal transcriptome changes.

Clinical investigation conducted in Russia produced a comparative trial against medazepam in subjects with generalized anxiety disorder and neurasthenia, results of which were published in 2008 [2]. Russian registration followed in 2009. Subsequent research has extended investigation into areas including enkephalin catabolism, stress-related neuroplasticity, and outcomes in alcohol-related cognitive and biochemical rodent models [6,7,11]. Further detail on the sourcing and verification standards for research-grade material is covered in the Selank sourcing and quality article, and research-grade Selank from SpartaLabs is verified by independent third-party analysis.

References

1. Myasoedov NF, Grigoriev VV, Gudasheva TA, Semenova TP, Skryabin AB, Ashmarin IP. A new generation of drugs: synthetic peptides based on natural regulatory peptides. Neuropharmacology. 2013. https://www.scirp.org/journal/paperinformation?paperid=40560

2. Zozulia AA, Neznamov GG, Syunyakov TS, Kost NV, Gabaeva MV, Sokolov OIu, Sebentsova EA, Akhromeeva SA, Panchenko LF, Andriushenko AV, Teleshova ES, Shadrina MI, Slominsky PA, Miasoedov NF. 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. PMID: 18454096.

3. Najjar VA, Nishioka K. "Tuftsin": a natural phagocytosis stimulating peptide. Nature. 1970;228(5272):672–673. https://doi.org/10.1038/228672a0

4. Andreeva LA, Myasoedov NF. Physiological effects of Selank and its fragments. Biology Bulletin. 2019;46(4):390–400. https://doi.org/10.1134/S1062359019040071

5. Semenova TP, Kozlovskaya MM, Zakharova NM, Kozlovskiy II. Intranasal administration of the peptide Selank regulates BDNF expression in the rat hippocampus in vivo. Doklady Biological Sciences. 2008;421:241–243. https://doi.org/10.1134/S0012496608040066

6. 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. https://doi.org/10.3389/fphar.2016.00031 PMC4757669.

7. Konstantinopolsky MA, Chernyakova IV, Poletaeva II, Zhukova II, Andreeva LA, Myasoedov NF. Selank, a peptide analog of tuftsin, attenuates aversive signs of morphine withdrawal in rats. Bulletin of Experimental Biology and Medicine. 2022;173(5):581–584. https://doi.org/10.1007/s10517-022-05624-x PMID: 36322304.

8. 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. PMID: 18577961.

9. 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. https://doi.org/10.1023/A:1024444321191 PMID: 14552529.

10. Semenova TP, Kozlovskaya MM, Zuikov AV, Kozlovskiy II, Myasoedov NF. Selank and short peptides of the tuftsin family in the regulation of adaptive behavior in stress. Neuroscience and Behavioral Physiology. 2003;33(9):853–860. https://doi.org/10.1023/A:1025988519919 PMID: 12154572.

11. Laukova M, Alaluf LG, Serova LI, Arango V, Sabban EL. Selank, peptide analogue of tuftsin, protects against ethanol-induced memory impairment by regulating BDNF content in the hippocampus and prefrontal cortex in rats. Bulletin of Experimental Biology and Medicine. 2019;167(5):641–644. https://doi.org/10.1007/s10517-019-04588-9