Selankresearch overview.

Overview

Selank is a synthetic heptapeptide, Thr-Lys-Pro-Arg-Pro-Gly-Pro. Its first four residues are tuftsin, a tetrapeptide that Najjar and Nishioka reported in 1970 as a fragment of immunoglobulin G that stimulated phagocytosis in their assays ¹. The remaining three residues are the same Pro-Gly-Pro extension used in Semax.

Selank was developed in Russia. Much of its literature comes from the Institute of Molecular Genetics of the Russian Academy of Sciences and collaborating Moscow institutes ⁵, and the same few senior authors appear on most of the papers ^2,5,7,8.

Published work has looked at enkephalin-degrading enzymes, GABA-related gene expression and receptor binding, behavioural measures in rodent stress models, and cytokine measures in small clinical studies ^2,4,5,7,8.

Structure and chemistry

Selank is a linear peptide of seven L-amino acids: Thr-Lys-Pro-Arg-Pro-Gly-Pro. Molecular formula C33H57N11O9, molecular weight 751.9 g/mol, CAS 129954-34-3. It has no D-amino acids, cyclisation or terminal capping groups.

The tuftsin core is short and strongly basic, with two cationic side chains (Lys and Arg). Adding Pro-Gly-Pro at the C-terminus follows the same design idea as Semax. Peptide bonds involving proline are cut by fewer common peptidases, so a proline-rich end is expected to slow breakdown compared with the parent sequence. For Semax this was tested directly in rat blood; a matching published comparison for Selank is not among the sources cited here.

Fragment studies give some insight into which parts of the sequence matter for a given assay. Kost et al. (2001) reported that inhibition of serum enkephalin-degrading enzymes was seen with the full heptapeptide and its pentapeptide fragments, but not with tri-, tetra- or hexapeptide fragments ². That pattern suggests the activity they measured depended on more than the tuftsin core alone.

Mechanisms investigated

As with Semax, no single receptor target has been confirmed. Published studies have tested several separate hypotheses in different systems.

• Enkephalin-degrading enzymes. In human serum in vitro, Kost et al. (2001) reported concentration-dependent inhibition of the enzymes that break down enkephalins, with both Selank and Semax ². A small Russian clinical study by Zozulia et al. (2008) later measured serum leu-enkephalin alongside rating scales ³.
• GABA-related gene expression. Volkova et al. (2016) used PCR arrays to measure 84 neurotransmission-related genes in rat frontal cortex 1 and 3 hours after Selank or GABA. They reported changes in 45 genes at 1 hour and 22 at 3 hours, and proposed allosteric modulation of the GABAergic system as one possible mechanism ⁵.
• Receptor binding. Vyunova et al. (2018) reviewed binding experiments and reported that Selank changed [3H]GABA binding in a way consistent with positive allosteric modulation ⁸.
• Cell model. In IMR-32 neuroblastoma cells, Filatova et al. (2017) found no direct effect of Selank alone on the GABAergic genes measured. When it was combined with GABA or with olanzapine, they reported changes in the gene-expression response to those compounds ⁶.
• Cytokines. In a small Russian clinical study, Uchakina et al. (2008) measured serum Th1/Th2 cytokine balance and IL-6 gene expression ⁴. This line connects to the immune activity reported for the parent peptide, tuftsin ¹.

Research areas

• Tuftsin, the parent tetrapeptide, in phagocytosis assays (historical, in vitro) ¹
• Enkephalin-degrading enzyme activity in human serum (in vitro) ²
• Neurotransmission gene expression in rat frontal cortex (animal) ⁵
• GABAergic gene expression in IMR-32 neuroblastoma cells (in vitro) ⁶
• Behavioural measures in a rat chronic mild stress model (animal) ⁷
• Radioligand binding and molecular mechanisms (review) ⁸
• Small comparative clinical studies with enkephalin and cytokine measures (human) ^3,4

Limits of the evidence

The published work comes from a small network of Russian research groups, with overlapping author lists across most of the papers cited here ^2,4,5,7,8. Independent replication by unrelated laboratories is limited.

The clinical reports are small, were published in Russian-language journals, and are hard to assess from their English abstracts alone ^3,4. This summary did not identify large, independently run randomised trials in the indexed literature.

The mechanistic findings come from very different systems: human serum, rat cortex and a human neuroblastoma cell line. They have not been combined into a single, tested mode of action, and some point in different directions. For example, the cell study saw no direct effect of Selank alone on the genes it measured ⁶, while the rat study reported broad changes ⁵.

OzPept’s Selank is a research chemical, not a medicine, and is not for human use.

Key studies

1. 2001In vitro

   Enkephalin-degrading enzymes in human serum ²

2. 2008Human

   Small comparative study with enkephalin measures ³

3. 2016Animal

   Neurotransmission gene expression in rat frontal cortex ⁵

4. 2017In vitro

   GABAergic gene expression in IMR-32 cells ⁶

5. 2017Animal

   Chronic mild stress model in rats ⁷

6. 2018Review

   Molecular mechanisms and GABA binding ⁸

Questions

References

1. Najjar VA, Nishioka K. "Tuftsin": a natural phagocytosis stimulating peptide. Nature. 1970;228:672-673. Source
2. Kost NV, Sokolov OI, Gabaeva MV, Grivennikov IA, Andreeva LA, Miasoedov NF, Zozulia AA. Semax and selank inhibit the enkephalin-degrading enzymes from human serum [in Russian]. Bioorg Khim. 2001;27(3):180-183. Source
3. Zozulia AA, 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(4):38-48. Source
4. Uchakina ON, Uchakin PN, Miasoedov NF, et al. Immunomodulatory effects of selank in patients with anxiety-asthenic disorders [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(5):71-75. Source
5. 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. Front Pharmacol. 2016;7:31. Source
6. Filatova E, et al. GABA, Selank, and olanzapine affect the expression of genes involved in GABAergic neurotransmission in IMR-32 cells. Front Pharmacol. 2017;8:89. Source
7. 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. Behav Neurol. 2017;2017:5091027. Source
8. Vyunova TV, Andreeva L, Shevchenko K, Myasoedov N. Peptide-based anxiolytics: the molecular aspects of heptapeptide Selank biological activity. Protein Pept Lett. 2018;25(10):914-923. Source