Semax vs Selank

How they differ structurally

Both peptides were developed at the Institute of Molecular Genetics of the Russian Academy of Sciences, and both were built by the same trick: pick a short fragment of a naturally occurring peptide with known central activity, then attach a Pro-Gly-Pro sequence to the C-terminus to slow enzymatic breakdown. The parent fragments, though, come from entirely different molecules.

Semax, CAS 80714-61-0, is a heptapeptide derived from the 4-10 region of adrenocorticotropic hormone, ACTH. The ACTH(4-10) fragment was already known to have effects on attention and learning in animal models without the hormonal activity of full-length ACTH, and Semax is that fragment with a methionine at the start and the Pro-Gly-Pro extension at the end. Its class is a synthetic ACTH fragment analogue. The Semax learn page has more on the ACTH fragment history.

Selank, CAS 129954-34-3, is also a heptapeptide, but its parent is tuftsin, a four-residue peptide that is a fragment of the Fc region of immunoglobulin G. Tuftsin was originally characterised for its effects on phagocytes, and Selank is tuftsin with the same Pro-Gly-Pro tail added. Its class is a synthetic tuftsin analogue. The Selank learn page covers the tuftsin background.

So the residue count is identical at seven, the C-terminal tail is identical, and the first four residues are completely different because they come from an adrenal-axis hormone in one case and an immunoglobulin fragment in the other. Both are linear, unmodified and water-soluble, and we stock each at 10mg.

Receptor and mechanism differences

Neither compound has a single well-defined receptor in the way a hormone analogue does, and the mechanism literature for both is more suggestive than definitive. That’s worth saying plainly before we describe what’s been proposed.

For Semax, the working hypothesis follows from its ACTH origin. The 4-10 fragment of ACTH is a melanocortin-derived sequence, and the published rodent work reports that Semax raises expression of brain-derived neurotrophic factor and its receptor TrkB in the hippocampus, and modulates gene expression in pathways related to neuronal survival and the immune response after ischemic injury. Some papers also describe effects on dopaminergic and serotonergic turnover. Whether any of that runs through melanocortin receptors, through a distinct binding site, or through a less specific membrane interaction is not resolved, and receptor binding data for Semax itself is sparse.

For Selank, the proposed mechanism is different in kind. Tuftsin’s biology is immunological, and the Selank papers describe effects on cytokine expression and on the balance of T-helper cell activity in animal models. On the neurological side, a Russian group reported that Selank alters expression of genes involved in GABAergic transmission and that it may act in part by modulating GABA-A receptor function, which is the basis for the anxiolytic-type effects described in rodent work. Some studies also report effects on enkephalin degradation. Again, direct receptor pharmacology is limited.

The practical summary is that Semax is discussed in terms of neurotrophic signalling and the melanocortin system, while Selank is discussed in terms of GABAergic and immune modulation. If you’re using either compound as a tool, the mechanism you’re probing is quite different.

What the literature compares

Most of the published work on both peptides is in Russian journals, with a smaller English-language body that has grown since the mid-2000s. That matters for planning, because a lot of the primary methods sections aren’t easy to get hold of in translation, and secondary summaries in English sometimes overstate what the primary papers showed.

Semax has been studied in rodent models of cerebral ischemia, in learning and memory tasks such as passive avoidance and maze tasks, in models of optic nerve injury, and at the level of gene expression in the hippocampus and cortex. It has a clinical history in Russia, where it is registered as a drug and has been studied in stroke and cognitive settings; that is a fact about the compound’s regulatory history in one country and says nothing about what a research vial is for.

Selank’s literature centres on anxiety-type behavioural models in rodents, on immune markers, and on gene expression related to GABAergic transmission. It also has a Russian registration as an anxiolytic. Head-to-head studies of the two in the same model exist but are few, and the ones we’ve seen tend to come from the originating institute, so independent replication is limited for both. If your design needs a direct comparison, expect to build it from separate literatures rather than from an established paired protocol.

Handling differences in the lab

There aren’t any meaningful differences. Both are short, linear heptapeptides with no lipid chains, no disulfides and no cyclisation, and they behave the same at the bench. Each arrives as a lyophilized powder in a sealed vial. Keep sealed vials at -20C and protected from light. When you reconstitute, use bacteriostatic water, add it slowly down the inside wall of the vial, and swirl gently until clear rather than shaking. Keep the vial sterile, label it with the compound, concentration and date, store the solution at 2-8C, use it within 28 days, and avoid freeze-thaw.

One thing that’s specific to Semax is the methionine at position one. Methionine is oxidation-prone, so a Semax solution that’s been left open to air or handled roughly may accumulate a methionine sulfoxide variant over time. It’s a small effect at the concentrations most labs work with, and the 28-day window is short enough that it rarely matters, but if you’re running mass spectrometry on your stocks you’ll want to know that a +16 mass shift is oxidation rather than contamination. Selank has no methionine and doesn’t have this concern. Both peptides dissolve readily, and ordinary polypropylene labware is fine.

Which to order for which research question

If your question is about neurotrophic signalling, BDNF-related gene expression, ischemic injury models or the melanocortin fragment literature, Semax is the compound to build around. It has the deeper published record in those areas and the ACTH(4-10) literature that predates it gives you additional context.

If your question is about anxiety-type behavioural models, GABAergic transmission, or the immunological effects of tuftsin-derived sequences, Selank is the one. It’s also the more interesting choice if you want to test the tuftsin parent against its stabilised analogue, because tuftsin itself is readily available and the comparison isolates what the Pro-Gly-Pro tail contributes.

Because both share the same C-terminal extension, ordering both lets you ask a structural question that neither alone can answer: how much of the observed activity in a given model comes from the Pro-Gly-Pro tail versus the parent fragment. A design that runs Semax, Selank and the free Pro-Gly-Pro tripeptide side by side would help clear that up, and to our knowledge it hasn’t been done thoroughly. Whichever you order, each lot is tested for HPLC purity, mass spectrometry identity and bacterial endotoxin, by a named third-party lab, with the lot COA on the product page, and the full certificate library is at /coas/. Both are >99% purity and vialed, finished, tested and shipped in the USA.