Selank 11 mg

Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro, written TKPRPGP in one-letter code. The first four residues reproduce tuftsin, a short endogenous peptide released by enzymatic cleavage from the heavy chain of immunoglobulin G. The remaining three residues, Pro-Gly-Pro, are a glyproline motif attached at the C-terminus. That tail is the entire structural difference between Selank and tuftsin, and it was added to slow cleavage of the parent tetrapeptide by exopeptidases.

The molecule is C33H57N11O9 with a monoisotopic mass near 751.4 and an average molecular weight of 751.9 g/mol. CAS 129954-34-3 designates the free peptide; the acetate salt carries a separate registry number and a correspondingly higher formula weight. Three of the seven residues are proline, which constrains the backbone and limits the conformational freedom typical of short linear peptides. The single lysine and single arginine give the molecule two basic side chains, so it carries a net positive charge at physiological pH. It contains no cysteine, no disulfide bridge and no non-standard residues; all seven positions are standard proteinogenic amino acids. Selank is supplied here as a lyophilised powder and is soluble in water.

The compound originates from the Institute of Molecular Genetics of the Russian Academy of Sciences in Moscow, where the tuftsin-plus-glyproline design was developed. Much of the pharmacological characterisation was carried out in collaboration with the Zakusov Research Institute of Pharmacology, also in Moscow. Selank was subsequently registered as a medicine in Russia in an intranasal form. It holds no marketing authorisation from the EMA or the FDA and is not an approved medicine in Europe. Material on this page is supplied for laboratory research use only.

The earliest mechanistic work on Selank concerns peptidase inhibition rather than receptor binding. Zozulya et al. (2001) measured enzymatic hydrolysis of enkephalin in human plasma and reported dose-dependent inhibition by Selank with an IC50 of 15 microM, describing the peptide as more potent in that assay than the peptidase inhibitors bacitracin and puromycin. The same report described a considerable shortening of enkephalin half-life and reduced total enkephalinase activity in blood during generalised anxiety, but not during panic disorder or agoraphobia. The authors proposed inhibition of enkephalin-degrading enzymes as a candidate mechanism.

A second strand of work examined gene expression in the GABAergic system. Volkova et al. (2016) administered Selank or GABA at 300 micrograms per kilogram to rats and profiled 84 neurotransmission-related genes in frontal cortex by real-time PCR. They reported significant expression changes in 45 genes at one hour after administration and in 22 genes at three hours, with a positive correlation between the Selank and GABA expression profiles at one hour. The authors described allosteric modulation of the GABAergic system as one possible molecular mechanism, and noted that the reported similarity between the physiological effect spectrum of Selank and that of classical benzodiazepines was the premise the study set out to test. Kasian et al. (2017) took a behavioural approach to the same question, testing Selank alone, diazepam alone, and the two together in the elevated plus maze under unpredictable chronic mild stress, and reported that the combination was the most effective of the conditions tested under chronic stress.

Neurotrophic signalling has been examined in a small number of rodent experiments. Inozemtseva et al. (2008) administered Selank intranasally to rats at 250 and 500 micrograms per kilogram and measured brain-derived neurotrophic factor in the hippocampus. They reported increased Bdnf messenger RNA three hours after administration and increased BDNF protein twenty-four hours after administration, at both doses. The authors read that pattern as stimulation of neurotrophic factor expression within hippocampal cells rather than axonal transport from remote areas of the brain. The report is short, confined to a single brain region, and has not been replicated independently of the originating group.

Monoamine work is limited but specific. Semenova et al. (2009) compared Selank with tuftsin in 87 mature Wistar rats pretreated with PCPA, an inhibitor of serotonin synthesis given at 320 mg/kg intraperitoneally four days before the experiment, and measured serotonin metabolism by brain region. Selank was reported to increase 5-HT metabolism in the brain stem 30 minutes after injection, while tuftsin induced no change in the brain stem and decreased 5-HT metabolism in the neocortex. That contrast between the parent tetrapeptide and the extended heptapeptide is one of the few direct head-to-head comparisons in the literature.

Human and immunological data come almost entirely from the originating groups. Uchakina et al. (2008) reported that Selank at 10^-7 M in vitro suppressed IL-6 gene expression in peripheral blood cells from patients but not from healthy controls, that IL-6 concentration rose in patient cell cultures in the presence of the peptide, and that shifts in the serum Th1/Th2 cytokine balance were found in patients who received Selank over 14 days. Zozulya et al. (2008) published a clinical evaluation in generalised anxiety disorder and neurasthenia in a Russian-language journal. The overall published record for Selank should be read with its limits in view: the great majority of primary studies originate from a small cluster of Moscow institutes, sample sizes are small, several key papers are available in English only as translated abstracts, and there is no large independent randomised placebo-controlled trial indexed in the English-language literature.