Semax 5mg

Semax is a synthetic seven-residue peptide, Met-Glu-His-Phe-Pro-Gly-Pro, in which residues 4 to 7 of adrenocorticotropic hormone (ACTH) are capped with a Pro-Gly-Pro tail. This listing is the 5 mg vial of freeze-dried powder, the main fill of the range; an 11 mg vial is also sold. Published work on Semax, most of it from Russian laboratories, has looked at neurotrophin expression in rat brain and cultured glial cells, and at how much of the peptide reaches brain tissue before it is broken down.

Specifications

Fills in this range

Semax is sold in 2 fills. The compound and the testing are the same in every fill; only the amount in the vial changes.

Which Semax this vial contains

The certificate gives the sequence as H-MEHFPGP-OH: seven residues with a free amino terminus and a free carboxyl terminus, formula C37H51N9O10S, theoretical mass 813.9 Da. That is the parent peptide. It is not N-acetyl Semax amidate, a modified compound sold under a similar name with an acetylated N-terminus and an amidated C-terminus. The modifications change its mass, so the LC-MS identity result on the certificate separates the two, and papers on one should not be read as evidence about the other.

In molar terms the vial holds about 6.1 µmol (5 mg at 813.9 Da), a little less once the water content reported on the certificate is allowed for. How Semax compares with Selank, its sister peptide with the same Pro-Gly-Pro tail, and what the amidate variants of both change, is covered in Semax vs Selank.

Handling notes: the methionine at position 1

Semax opens with methionine, the one residue in its sequence with an obvious oxidation route. Oxidation turns it into methionine sulfoxide, which leaves the chain in one piece but changes its mass and how it runs on RP-HPLC, so an oxidised lot looks different on both tests the certificate reports. Studies of methionine in proteins show how sensitive the reaction is to conditions: in granulocyte colony-stimulating factor the oxidation rate of each methionine changed with pH and with the motion of the surrounding chain¹. A seven-residue peptide has no fold to shelter its first residue.

Storage is therefore the main defence. Keep the sealed vial at −20 °C, desiccated and dark, and let it reach room temperature before opening so moisture does not condense on the powder. Once reconstituted, hold the solution at 2 to 8 °C, protected from light, for no longer than your laboratory has established. The general reasoning is in peptide storage and stability.

What the research covers

What Semax is

Semax was designed as an analogue of the ACTH(4-10) fragment². It keeps that fragment’s first four residues, Met-Glu-His-Phe, and in place of the remaining three carries Pro-Gly-Pro, a proline-rich tail added to slow breakdown by peptidases. The groups that developed and studied it describe marked effects on learning and neuroprotective activity in animals², and most of their mechanistic work concerns neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which govern the proliferation, differentiation and survival of neurons and glial cells³.

Cell culture: neurotrophin genes in glia

Shadrina and colleagues had seen Semax affect neuronal survival in vitro and suspected neurotrophic factors were involved³. They then exposed glial cells from the basal forebrain of newborn rats to Semax and tracked NGF and BDNF gene expression. Both rose within half an hour: at the 30-minute peak, BDNF mRNA was eight times the control level and NGF mRNA five times³. This was a culture study that measured mRNA, not protein.

Rat hippocampus: BDNF protein and trkB

In 2006 Dolotov and colleagues moved the question into living rats. After a single application of Semax, hippocampal BDNF protein rose to a maximum of 1.4 times control, phosphorylation of its receptor trkB rose 1.6-fold, and exon III BDNF mRNA and trkB mRNA rose threefold and twofold². The treated rats also made more conditioned avoidance reactions, and the authors proposed that Semax acts on learning through the hippocampal BDNF/trkB system². Quoting the threefold mRNA figure on its own overstates what happened to the protein, which changed far less.

How much reaches the brain

Shevchenko and colleagues labelled Semax with tritium at its C-terminal proline and followed it in rat brain and blood after nasal application⁴. Two minutes later, 0.093% of the total radioactivity per gram was found in the brain, and 80% of that brain radioactivity was intact Semax⁴. The peptide was degraded quickly, and the tripeptide Pro-Gly-Pro was the main species in the biological samples⁴. That study appeared in a Russian-language journal, Bioorganicheskaya Khimiya.

What is not established

Every Semax study cited here comes from Russian groups, and the two neurotrophin papers share an author, O. V. Dolotov²,³. None of the abstracts names the receptor that Semax itself binds, and none of the references with an available abstract reports a study in people. The rat work describes single applications and short time points. Because Pro-Gly-Pro outlasts the parent peptide⁴, effects measured later may involve fragments as well as intact Semax; the guide discusses reports that the tail has activity of its own. No paper here tested PrymaLab material. The wider picture, including how Semax differs from Selank and where the evidence is hard to check, is in the overview of peptides studied for brain and cognition.

The Semax vs Selank guide covers the literature in more depth.

How each lot is tested

Every lot is tested in PrymaLab’s own laboratory in Ashland, Kentucky before release: RP-HPLC for purity, LC-MS for identity, Karl Fischer titration for water, LAL for endotoxin and USP <71> for sterility. The results for the lot now shipping are in the certificate panel on this page, and the certificate number, key and QR code can be checked on the verify page. The one outside report on file is a Janoshik Analytical test of Semax 11 mg, batch 001 (task 96920, 99.39% purity), which can be checked on Janoshik’s verify page. These are in-house results from PrymaLab Analytical, not an independent test, and the lab is not accredited to ISO 17025. The third-party testing guarantee on this page still applies: if any independent laboratory finds the wrong compound, or less than the stated purity or amount, the order is refunded and the cost of the test is reimbursed.

Frequently asked questions

References

1. Chu JW, Yin J, Wang DI, et al. Molecular dynamics simulations and oxidation rates of methionine residues of granulocyte colony-stimulating factor at different pH values. Biochemistry. 2004;43(4):1019-29. DOI · PubMed
2. Dolotov OV, Karpenko EA, Inozemtseva LS, et al. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res. 2006;1117(1):54-60. DOI · PubMed
3. Shadrina MI, Dolotov OV, Grivennikov IA, et al. Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analog. Neurosci Lett. 2001;308(2):115-8. DOI · PubMed
4. Shevchenko KV, Nagaev IIu, Alfeeva LIu, et al. [Kinetics of Semax penetration into the brain and blood of rats after its intranasal administration]. Bioorg Khim. 2006;32(1):64-70. DOI · PubMed