What Has Published Research Reported About Selank?

What is Selank?

Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. The first four residues, Thr-Lys-Pro-Arg, are the sequence of tuftsin, a natural tetrapeptide, and the added Pro-Gly-Pro tail makes up the rest (source 9). The 2019 review by Koroleva and Myasoedov, from the Institute of Molecular Genetics of the Russian Academy of Sciences, described Selank as a peptide developed from tuftsin so that the native molecule’s activity could be combined with engineered features (source 11).

From the sequence, the formula can be calculated as C33H57N11O9, with a monoisotopic mass of 751.43 and an average mass of 751.88. For tuftsin the same arithmetic gives C21H40N8O6, 500.31 and 500.60. These are calculated values, not figures reported in a cited paper, and they are the numbers a laboratory would compare against a mass spectrum. This Steadfast Research Group profile covers the biochemical, cell, rodent and analytical literature. Clinical use is outside its scope.

Where did tuftsin come from, and what does it signal through?

Najjar and Nishioka reported tuftsin in a 1970 letter to Nature. They described a peptide produced in vitro from a leucophilic gamma-globulin fraction through the action of an enzyme they called leucokininase, and they ascribed the phagocyte-stimulating effect of that fraction to this single fragment, named for Tufts University (source 1).

A 2013 study by Nissen, Selwood and Tsirka examined tuftsin itself and reported that it bound the receptor neuropilin-1 on microglia and signaled through the TGF-beta receptor 1 coreceptor, with Smad3 phosphorylation increasing and Akt phosphorylation falling. The authors tied the anti-inflammatory M2 shift in microglia to that route, and an Nrp1 inhibitor, EG00229, blocked tuftsin binding (source 2). That work concerns tuftsin. The sources reviewed for this profile did not show that Selank acts through the same receptor, so the pathway should not be assumed to carry over.

What did enzyme studies report about Selank?

An early line of work looked at enkephalin-degrading enzymes. Kost and colleagues, in a 2001 paper in the Russian Journal of Bioorganic Chemistry, tested Semax and Selank against enkephalin-degrading enzymes of human serum. They reported IC50 values of about 10 micromolar for Semax and 20 micromolar for Selank, described as more pronounced than puromycin (IC50 10 mM), bacitracin and some other peptidase inhibitors. Pentapeptide fragments of the two heptapeptides also inhibited the enzymes, whereas the tri-, tetra- and hexapeptide fragments did not (source 3). This was an in vitro serum assay, and the abstract refers to the enzymes only as enkephalin-degrading enzymes of human serum.

A 2001 paper by Zozulya and colleagues in the Bulletin of Experimental Biology and Medicine carried the inhibition idea further, naming it in its title as “a possible mechanism of its anxiolytic activity” (source 4). The abstract text retrieved for this profile was too fragmentary to report its findings reliably, so it is cited at title level only. In 2019, Koroleva and Myasoedov summarized experimental and clinical data on Selank and its fragments and proposed that the peptide’s effects on a network of peptides and mediators run through enkephalin (source 11). That is a proposal in a review, not a direct measurement.

What did gene-expression studies report?

Most of the in vivo mechanistic work measured messenger RNA. In 2011, Kolomin and colleagues examined 84 inflammation-related genes in mouse spleen 6 and 24 hours after a single intraperitoneal administration of Selank or one of two fragments, using real-time PCR. They reported significant changes in the expression of dozens of those genes, and the Bcl6 gene changed after each of the peptides (source 5). A 2014 follow-up tracked the time course of four genes (C3, Casp1, Il2rg and Xcr1) after Selank and the dipeptide fragment Gly-Pro. The authors reported a significant change in Il2rg mRNA at early time points after both peptides and an almost equal fall in Xcr1 mRNA 90 minutes after each (source 6).

In 2016, Volkova and colleagues measured 84 neurotransmission-related genes in rat frontal cortex 1 and 3 hours after Selank or GABA. Expression changed in 45 genes at 1 hour and in 22 genes at 3 hours. The changes after Selank correlated positively with those after GABA at 1 hour and negatively at 3 hours, and the authors proposed that one possible molecular mechanism involves allosteric modulation of the GABAergic system (source 7). That conclusion was an interpretation of expression data and not a binding result.

A 2008 paper by Inozemtseva and colleagues in Doklady Biological Sciences asked whether Selank-induced changes in brain-derived neurotrophic factor (BDNF) expression, at mRNA and protein level, belong to the peptide’s central nervous system effects, using intranasal delivery in rats and the hippocampus as the tissue studied (source 10). Its figures are not reproduced here.

What did GABA receptor and cell studies report?

Vyunova, Andreeva, Shevchenko and Myasoedov reported in 2018 that Selank acted as a positive allosteric modulator of [3H]GABA binding in radioligand assays, with the authors concluding that the mechanism could involve subtype-selective, concentration-dependent allosteric modulation of GABA receptors. Selank blocked the modulatory effects of diazepam and olanzapine in the same assays, and the authors judged that the binding sites were not identical but might partly overlap (source 9). The paper’s title places the work under the heading “Peptide-based Anxiolytics” (source 9).

A cell-culture result pointed the other way. Filatova and colleagues, in 2017, studied 84 GABAergic and neurotransmission genes by qPCR in IMR-32 neuroblastoma cells and reported that Selank alone did not change the mRNA levels of the genes studied. Changes appeared mainly when Selank was combined with olanzapine, and the authors described the support for a Selank effect through GABA-A as only partial (source 8). Together with the rat cortex data (source 7), this shows how the mechanism depends on the system measured: a live-animal expression change did not reappear in one cultured neuroblastoma line.

How have analytical laboratories identified Selank?

Selank appeared in a forensic setting in 2020. Vanhee, Francotte, Janvier and Deconinck reported in Drug Testing and Analysis that two suspicious preparations seized in 2017 and 2018 were identified using high-resolution accurate-mass MS/MS, de novo peptide sequencing and confirmation against synthesized reference standards. One preparation matched Selank and a more hydrophobic one matched Semax. The authors noted that, to their knowledge, neither peptide had completed clinical trials, and their online search found such peptides sold as lyophilized powder and as nasal sprays (source 12).

The workflow is the same one laboratories use for any research peptide. The calculated [M+H]+ near 752.44 and [M+2H]2+ near 376.72 in the table above are the values a Selank spectrum would be checked against, and identity should be paired with a purity figure from a separate method. The guides to reading a peptide COA, mass spectrometry verification and HPLC purity testing cover those checks, and red flags when buying research peptides discusses the seizure literature more broadly.

What terms recur in the Selank literature?

Tuftsin

The natural tetrapeptide Thr-Lys-Pro-Arg, first described in 1970 and the N-terminal portion of Selank (sources 1 and 9).

Neuropilin-1 (Nrp1)

The receptor through which tuftsin was reported to signal on microglia (source 2).

Enkephalin-degrading enzymes

Peptidases that break down enkephalins, tested in a human serum assay (source 3).

IC50

The inhibitor concentration giving half-maximal inhibition, reported as about 20 micromolar for Selank in the serum assay (source 3).

Allosteric modulation

Binding at a site other than the main ligand site that changes the response, the mechanism proposed in sources 7 and 9.

Bcl6

A gene that changed after Selank and its fragments in mouse spleen (source 5).

What remains unresolved in the Selank literature?

Several limits apply. The mechanistic papers measured mRNA or in vitro binding, so they say little about protein levels or function in a living animal. Different systems gave different answers, as the cortex and neuroblastoma results show (sources 7 and 8). The fragment comparisons in sources 5 and 6 suggest that part of the activity may sit in the fragments, and the sources reviewed here did not separate the contribution of the intact peptide from that of its breakdown products.

Independence is also limited. Several authors recur across the papers, including Kolomin (sources 5 and 6), Shadrina (sources 5, 7 and 8) and Myasoedov (sources 5, 9 and 11), and the authors of sources 10 and 11 were listed at the Institute of Molecular Genetics. Some of the results above, such as the BDNF work and the enkephalinase finding in the 2001 bulletin paper, are cited here at design or title level because their figures could not be confirmed. This profile prints no animal or human amounts or schedules.