Semax vs Selank: structure, mechanism and research

How are Semax and Selank structurally similar?

Both peptides are seven residues long, and both end in the same three: Pro-Gly-Pro. Semax is Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP), formula C37H51N9O10S, molecular weight 813.9. Selank is Thr-Lys-Pro-Arg-Pro-Gly-Pro (TKPRPGP), formula C33H57N11O9, molecular weight 751.9. The formulas and weights are PubChem's (CIDs 9811102 and 11765600), and we recomputed both from the sequences.

The shared design reflects a shared origin. Most of the published work on Semax comes from groups at the Institute of Molecular Genetics of the Russian Academy of Sciences, and Selank was designed at the same institute together with the V.V. Zakusov Research Institute of Pharmacology. In each case a short, naturally occurring fragment was taken as the starting point and the Pro-Gly-Pro tripeptide was attached to its C-terminus. For Selank, its developers describe that extension as improving metabolic stability.

Which parent peptides are Semax and Selank built on?

Semax builds on the ACTH(4-7) fragment and Selank on tuftsin, two unrelated parents. The first four residues are where the two molecules part company. Semax keeps Met-Glu-His-Phe, the 4-7 segment of adrenocorticotropic hormone, and replaces the rest of the ACTH(4-10) fragment with Pro-Gly-Pro, which is why the papers call it an ACTH(4-10) analogue. Selank keeps Thr-Lys-Pro-Arg, which is tuftsin, a fragment of the human immunoglobulin G heavy chain.

The parents are unrelated, a pituitary hormone fragment in one case and an antibody fragment in the other, and the two literatures follow from that. Semax research is mostly about neurotrophins and brain gene expression; Selank research is mostly about the GABAergic system and immune gene expression. The Pro-Gly-Pro ending is common to both, but the Semax literature shows it is not simply inert: in a rat stroke model, Pro-Gly-Pro alone changed neurotrophin transcription in a partly overlapping pattern, which the authors judged mainly non-specific.

What models has Semax been studied in?

Semax has been studied mainly in rats, in two lines of work: BDNF in the uninjured brain and cerebral ischaemia models. One line of work looks at brain-derived neurotrophic factor (BDNF) in rats without brain injury. Dolotov and colleagues reported that a single application raised BDNF protein in the rat hippocampus by up to 1.4-fold, with increased phosphorylation of its receptor TrkB.

The other main line uses rat models of cerebral ischaemia. After permanent middle cerebral artery occlusion, Dmitrieva and colleagues reported increased transcription of neurotrophin and Trk receptor genes in ischaemic cortex, and a genome-wide study by Medvedeva and colleagues in the same model found that most of the genes Semax altered were immune-system genes, with a smaller vascular group. The product page summarises the rest, including later RNA-sequencing work and an in vitro amyloid aggregation study.

What models has Selank been studied in?

Selank has been studied mainly in rodent anxiety-like behaviour models and in gene-expression work centred on the GABAergic system. Behavioural work uses rodent anxiety-like behaviour models. Kasian and colleagues tested rats in the elevated plus maze, with and without unpredictable chronic mild stress, giving Selank and diazepam separately and together; without stress, either compound shifted anxiety-related measures, with smaller shifts after Selank.

Mechanistic work centres on GABAergic gene expression. Volkova and colleagues measured 84 neurotransmission-related genes in rat frontal cortex and found 45 with changed expression an hour after Selank or GABA, the changes after the two compounds positively correlated, with a few genes, including the dopamine receptor genes Drd1a and Drd2, changing only after Selank. Other studies in the same group look at inflammation-related genes in mouse spleen, a human neuroblastoma cell line and brain membrane binding assays; the product page covers them.

Both literatures, then, report changes in immune-related gene expression, but in different tissues and models: ischaemic rat brain for Semax, mouse spleen for Selank. The findings come from different tissues in unrelated models, so the overlap should not be read as a common mechanism.

What limits do the Semax and Selank literatures share?

The evidence for both peptides comes largely from one research network: closely connected groups in Moscow, many of them at or working with the Institute of Molecular Genetics. Among the papers we cite, the work from outside that network is the Catania amyloid study on Semax and the 2021 review by Doyno and White at the University of Connecticut, which describes Selank as a poorly studied Russian drug with GABAergic mechanisms.

Much of the work is in rodents, and much of the rest is in cell lines or membrane preparations. A good part is also published in Russian: in a PubMed search on October 20, 2026, 106 of the 233 records mentioning Semax and 33 of the 136 mentioning Selank were Russian-language. We cite only English-language papers we have read, so the summaries here and on the product pages are drawn from part of each literature, not all of it.

What does research on Semax and Selank not show?

Neither literature compares the two peptides directly. We found no study that tests Semax and Selank side by side in the same model, so nothing here supports ranking one above the other, in any model or in people. Papers from the Moscow groups refer to clinical studies in Russia; we have not reviewed those and do not summarise them.

Neither literature establishes a mechanism. The pathways proposed for each, neurotrophin signalling for Semax and allosteric modulation of GABA-A receptor binding for Selank, come from individual models, and the authors describe them as proposals. Gene-expression changes in a rat brain region an hour after one application say what changed in that tissue, not what the change does.

What do the Semax and Selank certificates cover?

Both certificates report purity and heavy metals, but neither includes a mass-spectrometry identity test. The two certificates come from different laboratories and test different things. The Semax certificate, lot 20250510, is from North South Precision Testing in China and reports 99.75% purity alongside impurities, heavy metals (Pb, Cd, Hg, As), moisture, pH and solubility; it names the compound and its CAS number but contains no mass-spectrometry identity test, and the laboratory states that the sample information was supplied by its client. The Selank certificate, lot ABL-SEL-2605, is from Vanguard Laboratory and reports purity above 99.80% by HPLC-UV/VIS, plus heavy metals by ICP-MS, endotoxin by LAL and microbial limits under USP <61>.

Selank's certificate covers contaminants that Semax's does not, but neither includes a mass-spectrometry identity check, so neither confirms by mass that the vial holds the sequence on the label. For why that distinction matters, see HPLC vs mass spec: what each test proves and How to read a peptide certificate of analysis; every certificate we hold, with its laboratory and tests, is in the COA library. Other compounds in this area are listed under Neuropeptide.

References

1. Dolotov OV, Karpenko EA, et al. (2006). Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res. [RODENT] PubMed record for reference 1, Dolotov 2006
2. Dmitrieva VG, Povarova OV, et al. (2010). Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. Cell Mol Neurobiol. [RODENT] PubMed record for reference 2, Dmitrieva 2010
3. Medvedeva EV, Dmitrieva VG, et al. (2014). The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. BMC Genomics. [RODENT] PubMed record for reference 3, Medvedeva 2014
4. Volkova A, Shadrina M, Kolomin T, et al. (2016). Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission. Front Pharmacol. [RODENT] PubMed record for reference 4, Volkova 2016
5. Kasian A, Kolomin T, Andreeva L, et al. (2017). Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats. Behav Neurol. [RODENT] PubMed record for reference 5, Kasian 2017
6. Doyno CR, White CM (2021). Sedative-Hypnotic Agents That Impact Gamma-Aminobutyric Acid Receptors: Focus on Flunitrazepam, Gamma-Hydroxybutyric Acid, Phenibut, and Selank. J Clin Pharmacol. [REVIEW] PubMed record for reference 6, Doyno 2021

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