Semax

What is Semax?

Semax was synthesised at the Institute of Molecular Genetics of the Russian Academy of Sciences under I.P. Ashmarin and N.F. Myasoedov. It keeps residues 4–7 of adrenocorticotropic hormone (ACTH), Met-Glu-His-Phe, and replaces the rest of the 4–10 region with Pro-Gly-Pro, a tripeptide that makes it resistant to peptidases. That is why it is usually described as an ACTH(4-10) analogue. It does not include the part of ACTH responsible for its hormonal activity.

Selank uses the same Pro-Gly-Pro tail on a different starting fragment (tuftsin). The two are compared in Selank vs Semax.

Semax identity

Semax vs N-acetyl Semax amidate

“N-acetyl Semax amidate” is a different molecule: Semax with an acetyl group on the N-terminus and an amide on the C-terminus (Ac-MEHFPGP-NH₂, C₃₉H₅₄N₁₀O₁₀S, 855.0 g/mol, PubChem CID 172638603). We found no peer-reviewed study of that exact form, and the published Semax literature below is about unmodified Semax. This product is unmodified Semax.

Certificate for the current lot

The current Semax lot was analysed by ILS Laboratories in San Diego, which states ISO/IEC 17025 accreditation for activities within its published scope:

How Semax has been studied

• Binding and BDNF (rats, 2006). Tritium-labelled Semax bound specifically, reversibly and calcium-dependently to rat basal-forebrain membranes (K_D 2.4 nM). Intranasal Semax raised BDNF protein in the basal forebrain within three hours, but not in the cerebellum. Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. Dolotov OV, et al. Journal of Neurochemistry, 2006.
• BDNF and trkB in the hippocampus (rats, 2006). A single application gave a 1.4-fold rise in hippocampal BDNF protein and a 1.6-fold rise in trkB phosphorylation. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Dolotov OV, et al. Brain Research, 2006.
• Monoamine systems (rodents, 2005). Semax raised striatal serotonin metabolite (5-HIAA) and, given before D-amphetamine, enhanced the amphetamine-induced rise in extracellular dopamine. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Eremin KO, et al. Neurochemical Research, 2005.
• Focal ischaemia transcriptome (rats, 2014). In a permanent middle-cerebral-artery occlusion model, more than half the genes Semax altered were immune-system genes, with further changes in vascular genes. The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. Medvedeva EV, et al. BMC Genomics, 2014.
• Human imaging (2020). A resting-state fMRI study in 52 healthy participants compared Semax, Selank and placebo and reported effects on amygdala–temporal-cortex connectivity, some shared by both peptides and some specific to each. Functional Connectomic Approach to Studying Selank and Semax Effects. Panikratova YR, et al. Doklady Biological Sciences, 2020.

Clinical studies of Semax are Russian, mostly in stroke rehabilitation, and mostly published in Russian; ClinicalTrials.gov lists none. The developers’ own 15-year review describes its use in Russian clinical practice. Asmarin (Ashmarin) IP, et al., 1997; Gusev EI, et al., 2018.

Regulatory status

A 2022 review lists Semax among the peptide products registered in the Russian Federation, as a nootropic. In the US it is not an approved drug; FDA’s compounding safety-risk page lists “Semax (heptapeptide)” among nominated-but-withdrawn substances and notes limited safety information. Deigin VI, et al. Pharmaceutics, 2022; FDA compounding safety-risk list. Clean Peptide’s Semax is a laboratory reference material only.

Related research

• Semax Spray: the same peptide, 20 mg in a 20 mL spray bottle, already in solution.
• Selank and Selank Spray: the tuftsin glyproline.
• Selank vs Semax.
• All neuropeptides.