Semax and Selank: Two Russian-Developed Neuropeptides

Semax and Selank are two synthetic heptapeptides developed at the Institute of Molecular Genetics of the Russian Academy of Sciences, each constructed by attaching the tripeptide Pro-Gly-Pro to a short parent fragment of known biological interest — ACTH(4–7) in the case of Semax, the IgG-derived tetrapeptide tuftsin in the case of Selank. Neither peptide is approved by FDA. Both are supplied for laboratory research use only and are not for human or animal consumption.

A shared design principle

The two compounds are more usefully understood as products of one design strategy than as alternatives to each other. In the Russian literature the PGP extension is described as increasing resistance to enzymatic degradation, and PGP has itself been studied as a separate fragment — the VEGF-family ischaemia study cited below runs Semax and PGP as parallel arms specifically to separate the contributions. In the case of Semax, the extension is also described as removing the steroidogenic activity of the parent hormone fragment. Those are design rationales reported by the originating groups, not independently established pharmacology.

Specifications

Mechanism and study-model comparison

Semax: parent sequence and reported mechanisms

Semax corresponds to ACTH(4–7) extended by Pro-Gly-Pro. The mechanistic literature is dominated by expression endpoints in rodents. Shadrina et al. (2001) treated glial cell cultures derived from the basal forebrain of newborn rats and reported elevation of NGF and BDNF messenger RNA. Dolotov et al. (2006) reported specific, time-dependent and reversible binding of tritium-labelled Semax in rat basal forebrain tissue, together with an increase in BDNF protein in the same region within hours. Medvedeva et al. (2014) applied genome-wide transcriptional analysis to rat cerebral cortex in a focal ischaemia model and reported differential expression concentrated in gene sets related to immune and vascular function; the same group extended that analysis to immune response genes in 2017, and had earlier compared Semax against its C-terminal PGP fragment on VEGF-family gene expression in the same model. Outside the animal literature, Kost et al. (2001) reported concentration-dependent inhibition of enkephalin-degrading enzymes by both Semax and Selank in human serum in vitro, with reported IC₅₀ values on the order of 10 µM for Semax and 20 µM for Selank.

Taken together, that record describes transcriptional and neurotrophin-related responses in specified rodent and in vitro systems. It does not identify a receptor, and it does not establish a mechanism in humans.

Selank: parent sequence and reported mechanisms

Selank is tuftsin extended by the same Pro-Gly-Pro tripeptide. Tuftsin itself is a naturally occurring fragment of the immunoglobulin G heavy chain associated with phagocyte function, which is why parts of the Selank literature examine immune tissue alongside brain tissue. Inozemtseva et al. (2008) reported that intranasal Selank altered Bdnf messenger RNA and BDNF protein levels in the rat hippocampus in vivo, assessed by reverse-transcriptase PCR and immunoassay. Kolomin et al. (2010) applied microarray profiling to rat hippocampus and spleen after single and chronic administration and reported altered messenger RNA levels across a few dozen genes in each condition. Volkova et al. (2016) profiled an 84-gene neurotransmitter receptor and regulator panel in rat frontal cortex, reporting expression changes in 45 genes at one hour and 22 genes at three hours after administration of either Selank or GABA, and noting a positive correlation between the two expression profiles at the one-hour point — a result the authors read as consistent with an effect on GABAergic signalling. A 2017 follow-up in the same journal extended that comparison to IMR-32 human neuroblastoma cells. Selank also appears alongside Semax in the Kost et al. (2001) enkephalin-degrading enzyme work.

A body of Russian-language human clinical literature on Selank was published in the 2000s and formed part of the basis for its domestic registration. That work is largely absent from English-language indexes, has not been independently replicated outside Russia, has not been reviewed by FDA, and is not a basis for any use of research-grade material.

What the comparison does and does not establish

Both literatures share the same structural limitations. The published record for each peptide originates largely from a small number of affiliated institutes in Moscow. The dominant endpoints are messenger RNA and protein expression rather than functional outcomes, and expression changes across dozens of genes are hypothesis-generating rather than mechanism-defining. Neither compound has a confirmed receptor, and neither has been through Western regulatory review. Outside the in vitro enzyme work cited above, the two peptides have seldom been examined head-to-head in a single well-powered study, so no ranking between them can be drawn from the literature, and none is offered here.

Regulatory status

Semax and Selank are both registered as medicines in the Russian Federation. Registration in one jurisdiction is not FDA approval and is not evidence of safety or efficacy under FDA standards. In the United States neither peptide is FDA approved, neither is a dietary ingredient, and neither may lawfully be sold or represented for human use. Both are supplied here strictly as research chemicals under our research use policy and are not for human or animal consumption. FDA's Category 1 and Category 2 bulk drug substances lists for compounding are revised periodically; the current FDA listing is the authoritative source for the status of any given peptide and should be consulted directly.

Handling and documentation

Both peptides are supplied lyophilized and are handled as ordinary synthetic heptapeptides: stored desiccated at −20 °C, protected from light and moisture, and equilibrated to ambient temperature before opening to limit condensation on cold powder. Semax carries a methionine residue at position one, and methionine is among the residues most prone to oxidation in peptide storage — a reason to keep vials sealed, dry and dark. Cold-chain and shelf-life guidance is collected under peptide storage, laboratory preparation of stock solutions under reconstitution, and the associated concentration arithmetic in the peptide calculator. Identity and purity for a given lot come from the certificate of analysis, not the catalogue page; lab testing explains what HPLC and mass spectrometry reports establish.

How are these peptides stored?

As lyophilized powder, desiccated at −20 °C and protected from light and moisture. Prepared solutions are less stable than sealed powder, and repeated freeze–thaw cycling is a common cause of degradation in short peptides.

Are Semax and Selank chemically related?

They share the C-terminal Pro-Gly-Pro tripeptide and the same design logic, but their parent fragments are unrelated: ACTH(4–7) for Semax, tuftsin for Selank. They are distinct molecules with distinct molecular formulas and masses.

What should a certificate of analysis confirm?

A lot-specific report showing HPLC purity, a mass spectrometry result matching the expected molecular weight for the named sequence (813.9 g/mol for Semax, 751.9 g/mol for Selank), and the identity of the analysing laboratory. A generic or undated report is not lot documentation.

Does registration in Russia change the regulatory status in the United States?

No. Foreign registration confers no FDA status. Neither peptide is FDA approved, and material supplied here is for laboratory research only, not for human or animal consumption.