Two short Pro-Gly-Pro-stabilized peptides from the Russian Academy of Sciences: what the rat, in vitro and clinical studies of Semax and Selank actually report, where the evidence is thin, and how to handle the material in the lab.
Selank and Semax are short synthetic peptides developed at the Institute of Molecular Genetics of the Russian Academy of Sciences in Moscow. Most of the studies cited in this guide come from that institute and its collaborators, which is worth keeping in mind as you read them. Both peptides were built on the same idea: take a brief fragment of a natural regulatory peptide and add a Pro-Gly-Pro tail to slow its breakdown. This guide covers where each one came from, what the animal, cell and clinical literature reports, where that evidence is thin, and how to handle the material in the lab.
Semax is the heptapeptide Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP, 813.93 Da). It is usually described as an analog of the adrenocorticotropin fragment ACTH(4-10) [1]. Structurally, its first four residues are ACTH(4-7) and the remaining three are the added Pro-Gly-Pro tripeptide [3]. The goal was a short molecule that keeps the neurotropic activity attributed to ACTH(4-10) and survives longer in biological fluids.
Selank is Thr-Lys-Pro-Arg-Pro-Gly-Pro (TKPRPGP, 751.87 Da). Its first four residues are tuftsin, a tetrapeptide cleaved from immunoglobulin G by two enzymes, one in the spleen and one on the outer surface of phagocytic cells. Tuftsin was characterized as a natural activator of phagocytes, stimulating phagocytosis, motility and related functions [7]. Selank therefore sits at the border of immunology and neuroscience, and both sides show up in its literature.
Short linear peptides are cleared quickly by peptidases. In rat serum, aminopeptidases and angiotensin-converting enzyme accounted for most of the hydrolysis of both ACTH(4-10) and Semax; the aminopeptidase inhibitor bestatin blocked up to 66% of total degrading activity [6]. The tail is not inert, however. In a rat stroke model, Pro-Gly-Pro given on its own also increased transcription of several neurotrophin genes, although the authors judged its effect to be mostly nonspecific, while Semax acted selectively in the ischemic cortex [3]. Any experiment that attributes an effect to Semax or Selank is stronger with a Pro-Gly-Pro-only control.
A key mechanistic study is a 2006 rat experiment in which Semax was applied intranasally once. In the hippocampus, BDNF protein rose by up to 1.4-fold and trkB tyrosine phosphorylation by 1.6-fold, while exon III BDNF mRNA rose 3-fold and trkB mRNA 2-fold. Animals given Semax also made more conditioned avoidance reactions, and the authors proposed that Semax influences learning through the hippocampal BDNF/trkB system [1]. The study is useful because it measured protein and receptor activation, not only transcripts. Note the gap between the mRNA and protein changes: a 3-fold transcript rise translated into a 1.4-fold protein rise.
Most of the neuroprotection work uses permanent middle cerebral artery occlusion in rats. In one study, Semax increased transcription of Bdnf, TrkC and TrkA in the cortex 3 hours after occlusion, Nt-3 and Ngf at 24 hours, and Ngf again at 72 hours [3]. A genome-wide transcriptional analysis of the same model found that the genes Semax altered were predominantly immune-related: by 24 hours they made up more than half of all Semax-responsive genes, led by immunoglobulin and chemokine genes. Twenty-four vascular-system genes changed at 3 hours and twelve at 24 hours [4]. The authors proposed that immune and vascular effects may underlie the neuroprotection they observed. That is a hypothesis drawn from expression data, and it still needs functional testing.
In rodent neurochemistry experiments, Semax increased striatal tissue levels of the serotonin metabolite 5-HIAA by 25% at 2 hours, and extracellular 5-HIAA rose gradually to 180% of baseline over 1 to 4 hours. Semax alone did not change dopamine or its metabolites, but given 20 minutes before D-amphetamine it markedly enhanced amphetamine's effect on extracellular dopamine and on locomotor activity [5]. So the dopaminergic effect reported here is modulatory, not a direct release of dopamine, which matters when choosing readouts.
Russian authors describe Semax as being used clinically in Russia for acute stroke [3]. The clinical study in our bibliography compared 30 patients with acute hemispheric ischemic stroke who received Semax alongside standard care with 80 patients of similar severity who received conventional care only. The authors reported some effect on the rate at which neurological function recovered, especially motor function [2]. The abstract does not describe randomization or blinding, and the paper is in Russian, so it is best read as early clinical observation. Semax is not approved by the U.S. FDA.
One proposed mechanism for Selank involves the enkephalins. In blood from patients with generalized anxiety disorder, enkephalin half-life was shortened. In vitro, Selank inhibited the enzymatic breakdown of plasma enkephalin with an IC50 of 15 µM, and it was more potent than the peptidase inhibitors bacitracin and puromycin. From this, the authors proposed enkephalinase inhibition as a basis for Selank's anxiolytic activity [8].
A 2016 rat study measured 84 neurotransmission-related genes in the frontal cortex 1 and 3 hours after Selank or GABA. Forty-five genes changed at 1 hour and 22 at 3 hours, and the changes produced by Selank correlated positively with those produced by GABA [9]. The authors suggested that Selank may act partly through allosteric modulation of the GABAergic system. That conclusion rests on patterns of gene expression, not on receptor binding or electrophysiology, so it remains a working hypothesis.
The same Moscow group that described Semax's effect on hippocampal BDNF also reported that intranasal Selank regulates BDNF expression in the rat hippocampus [10]. In a developmental model, rats whose catecholamine neurons were damaged with 6-hydroxydopamine during the first three days of life showed impaired learning, memory and attention as adults. In those animals, Selank restored the impaired cognitive measures [11].
In a Russian clinical study of 62 patients with generalized anxiety disorder or neurasthenia, 30 received Selank and 32 received the benzodiazepine medazepam. On the Hamilton, Zung and CGI scales, the two drugs had similar anxiolytic effects, and the authors reported additional anti-asthenic and stimulant-like effects with Selank. Leu-enkephalin half-life, which was low at baseline, increased during the study in the Selank group [12]. The study used an active comparator, and the abstract does not describe a placebo arm. Selank is not approved by the U.S. FDA.
The models in this literature are fairly consistent. They include permanent middle cerebral artery occlusion in rats, analyzed by targeted qPCR [3] or genome-wide arrays [4]; conditioned avoidance learning paired with hippocampal BDNF protein and trkB phosphorylation measurements [1]; striatal microdialysis for monoamines and their metabolites [5]; neonatal 6-hydroxydopamine lesions followed by adult cognitive testing [11]; qPCR panels of neurotransmission genes [9]; and in vitro enzyme assays using plasma enkephalins [8]. For new work, the strongest designs pair a transcript readout with protein-level or functional confirmation, include Pro-Gly-Pro and parent-fragment controls, and confirm the intact peptide by HPLC or LC-MS in the test matrix.
Both peptides are supplied as white lyophilized powders. They should be stored sealed at -20°C and are soluble in sterile water. Let the vial come to room temperature before opening so that condensation does not form on the powder. If the material will be used across several experiments, divide solutions into single-use aliquots rather than freezing and thawing a stock repeatedly. Semax begins with methionine, which can oxidize to methionine sulfoxide and appears in mass spectrometry as a +16 Da species. Selank contains neither methionine nor cysteine. Northbridge Research Labs has every batch tested by an independent third-party lab. The certificate for Selank lot SK100001 (10 mg, 99.83% purity, tested August 2026) is published on our COA page.
Note: Selank and Semax are sold by Northbridge Research Labs for laboratory research use only. They are not for human or veterinary use, and this article describes published research only.
Studied compound
Semax
The same material this research covers — 99%+ purity, independently tested, with the certificate for each batch published online.
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