Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro, created as a stabilized analog of the adrenocorticotropic hormone fragment ACTH(4–10). The molecule was developed in the 1980s at the Institute of Molecular Genetics of the Academy of Sciences (the group of M. F. Myasoedov and I. P. Ashmarin) to reproduce the neurotropic effects of melanocortins without their hormonal activity. It was first described in the scientific literature in the early 1990s.
The key structural idea of Semax is attaching the C-terminal tripeptide Pro-Gly-Pro (PGP) to the active core ACTH(4–7). This motif shields the peptide from rapid cleavage by proline-specific peptidases, extending its duration of action compared with the native ACTH fragment. This page is for reference and describes the compound as a subject of laboratory research.
What it is and its class
By chemical classification Semax belongs to the short regulatory peptides, analogs of melanocortins. It lacks the steroidogenic (hormonal) activity of full-length ACTH but retains a large part of its neurotropic properties. In a research context the compound is grouped among nootropic and neuroprotective agents. The molecular formula is C37H51N9O10S, the molar mass about 813.9 g/mol, and the CAS (Chemical Abstracts Service) number 80714-61-0.
Mechanism of action
The main line researchers study is the effect of Semax on the neurotrophin system. In rodent models a single injection of the peptide raised the mRNA and protein levels of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor TrkB in the hippocampus and basal forebrain [1][3]. Specific binding of Semax to brain tissue that precedes the rise in BDNF has also been shown [3].
Under experimental ischemia, Semax and its fragment PGP activate transcription of BDNF and also of nerve growth factor (NGF), neurotrophin-3 (NT-3) and the corresponding receptors (TrkA, TrkB, TrkC) in the cerebral cortex [2]. Transcriptomic studies after ischemia-reperfusion show that the peptide modulates broad groups of genes linked to inflammation, immune response and vascular processes [4]. Additional mechanisms under discussion include antioxidant and anti-inflammatory action and an effect on melanocortin receptors, though the precise molecular details remain under study.
What the research shows
The largest body of data concerns cerebral ischemia models. In rats with middle cerebral artery occlusion, administration of Semax was associated with a change in neurotrophin expression in the time window when neuroprotection is most critical [2][4]. This work forms the molecular basis for the hypothesis of a protective role for the peptide in acute cerebrovascular events.
A separate direction is cognitive and neuroplastic effects: behavioral models examined the influence on learning and memory, which is linked to BDNF/TrkB signaling [1]. Clinical studies of Semax were conducted mainly within Russian medical practice (ischemic stroke, hypoxia-related conditions), but these data come largely from small samples and outside international regulatory procedures, so they call for cautious interpretation and independent replication. The directions given here describe experimental observations, not proven clinical efficacy.
Form and handling (research-use)
Longeva supplies Semax solely as a research substance (reagent) with an accompanying certificate of analysis (COA). It is not a medicine and is not intended for diagnosis or treatment. The typical supply form is a lyophilized powder, which in laboratory practice is reconstituted in a suitable solvent. The lyophilizate is stored frozen and protected from light and moisture; reconstituted solutions are held briefly at +2…+8 °C. Like any peptide with methionine and histidine residues, Semax is sensitive to oxidation, so repeated freeze-thaw cycles should be avoided. The compound should be handled by qualified researchers following good laboratory practice.