Semax Research Peptide

What is Semax?

Semax has no common alias. It’s a heptapeptide, seven amino acids, with the CAS number 80714-61-0, and it belongs to the class of synthetic ACTH fragment analogues. The sequence comes from the 4-10 region of adrenocorticotropic hormone, the stretch Met-Glu-His-Phe-Arg-Trp-Gly, which had been known since the 1970s to have effects on attention and learning in animals that are separate from ACTH’s job at the adrenal gland. The Russian group at the Institute of Molecular Genetics in Moscow, working under Ashmarin and later Myasoedov, kept the first four residues of that fragment and replaced the tail with Pro-Gly-Pro, a change that made the peptide far more resistant to the enzymes that clear the native fragment in minutes.

Semax was registered as a drug in Russia, supplied as a nasal solution, and most of the clinical literature comes from there. Researchers outside Russia order it because it’s a well-characterized tool for neurotrophic and behavioral models, and because so little of the Western work has tried to replicate the Russian findings. We stock it as a 10mg lyophilized vial at the Semax product page.

Structure and mechanism

The mechanism of Semax is less clean than a receptor agonist’s, and it’s fair to say the field is still arguing about it. Native ACTH 4-10 has weak affinity for melanocortin receptors, and the obvious hypothesis was that Semax worked the same way, but the Pro-Gly-Pro substitution removes the residues that melanocortin receptors most depend on, and binding studies haven’t supported a strong melanocortin story. What the published work does show, repeatedly, is that Semax raises expression of brain-derived neurotrophic factor and its receptor TrkB in rat hippocampus and basal forebrain, and that it changes the expression of a broad set of genes tied to the immune and vascular response after experimental stroke in rats.

A Russian group reported specific binding sites in rat basal forebrain membranes in 2006, though the identity of that site hasn’t been pinned down. Our honest summary is that it has a reproducible effect on neurotrophin expression in rodents, and the receptor-level explanation for that effect is still open. If your experimental question needs a defined molecular target, that’s a limitation worth designing around.

What the published research covers

Most of the primary literature is Russian, and a good deal of it was published in Russian-language journals before being summarized in English reviews. The preclinical work falls into a few buckets. There’s a large body of rodent behavioral work on attention, learning and memory tasks, going back to the original ACTH-fragment studies, and the neurotrophin work described above sits alongside it. The ischemia work is mostly rat middle cerebral artery occlusion models, looking at infarct-related gene expression and functional recovery, and a smaller set of studies covers the retina and optic nerve in animal models.

The clinical literature from Russia includes trials in ischemic stroke and in optic nerve disease, run under the Russian registration, and those are facts about the literature rather than results anyone should expect to reproduce. Outside Russia the record is close to empty: a few in vitro studies and almost no independent replications of the behavioral findings. That gap is, for a lot of the researchers we talk to, the reason they order it. If you’re weighing it against Selank, the two are compared structurally and by literature at Semax vs Selank.

Reconstitution and handling

Semax arrives as a lyophilized powder in a sealed septum vial. Let it warm to room temperature before you open it so no condensation forms on the cake, then swab the stopper and let the alcohol flash off. A seven-residue peptide dissolves quickly, and the main thing you’re managing is the methionine at position one, which will oxidize if it’s given the chance; that’s a reason to work briskly and to keep the vial closed between steps. For diluent we recommend bacteriostatic water when the vial will be entered more than once, and sterile water if you’re making a single working solution and using it the same day.

Add the water down the inside wall, swirl gently until the solution is clear, and don’t shake. The solution should be colorless and free of particles; if it’s not, set that vial aside. Label it straight away with the compound, lot number, the concentration you prepared and the date. Use a fresh sterile needle for every entry, and record the volume you’ve removed so the remaining stock is traceable back to the lot on the COA.

Storage and stability

The sealed lyophilized vial belongs at -20C, protected from light, and it’s stable there for a long time. Once it’s in solution, keep it at 2-8C, and treat 28 days as the working limit for a vial reconstituted with bacteriostatic water. Semax has two features that make us conservative here. The N-terminal methionine is oxidation-prone, and methionine sulfoxide is a different molecule that may or may not behave the same way in your assay; the literature is thin on whether it does. And the Pro-Gly-Pro tail, while it resists the peptidases the native fragment falls to, doesn’t make the molecule immune to everything in a solution that’s been open for weeks.

Avoid freeze-thaw. If you need reconstituted stock for longer than a month, aliquot on day one into single-use tubes and freeze those, thawing each once. For dilute working solutions, use low-binding tubes, since a small peptide at low concentration can lose a meaningful fraction of itself to the wall of an ordinary polypropylene tube.

How it’s tested

Each lot of Semax is released only after HPLC purity, mass spectrometry identity and bacterial endotoxin, by a named third-party lab, with the lot COA on the product page. The purity spec is >99% by HPLC. Mass spectrometry matters more for Semax than for some peptides because the oxidized form differs from the intact peptide by a single oxygen, and a chromatogram alone can be ambiguous about whether a small shoulder peak is the sulfoxide or something else; the mass makes it unambiguous. Endotoxin is tested because Semax mostly goes into neuronal cultures and animal models where bacterial residue would produce its own inflammatory signal and swamp the effect you’re measuring.

When you read the certificate, confirm the lot number against your vial, look for a single dominant HPLC peak with the purity written as a number, check the observed mass against the expected value for Semax, and check that endotoxin is reported as a value below the limit. All of our certificates are collected at /coas/, and every vial is vialed, finished, tested and shipped in the USA. Orders process within 1 business day.