Semax, CAS 80714-61-0, derives from adrenocorticotropic hormone. It is usually described in the literature as an ACTH(4-10) analog, and structurally it is the ACTH(4-7) tetrapeptide Met-Glu-His-Phe carrying a carboxy terminal Pro-Gly-Pro extension. Selank, CAS 129954-34-3, derives from tuftsin, a tetrapeptide released from the immunoglobulin G heavy chain, and carries the same Pro-Gly-Pro extension on Thr-Lys-Pro-Arg. It is catalogued as TP-7.
Both are seven residues long. Semax is H-Met-Glu-His-Phe-Pro-Gly-Pro-OH, formula C37H51N9O10S, average mass 813.92. Selank is H-Thr-Lys-Pro-Arg-Pro-Gly-Pro-OH, formula C33H57N11O9, average mass 751.88. The gap of roughly sixty two daltons comes mostly from the methionine and histidine in Semax set against the lysine and arginine in Selank. Semax is the only one of the two that contains sulfur. Selank is markedly more basic, carrying both a lysine and an arginine, which affects solubility behaviour and how readily the peptide adsorbs to acidic surfaces during handling.
In the published literature the two are studied along different lines. Rodent work on Semax reports changes in brain derived neurotrophic factor and nerve growth factor expression, along with effects on dopaminergic and serotonergic markers, and notes that the fragment lacks the corticotropic activity of the parent hormone. Rodent work on Selank reports interactions with GABAergic signaling, inhibition of enkephalin degrading enzymes, and changes in interleukin and interferon gene expression in immune tissue. Neither line of work has been consolidated into a single accepted mechanism.
The shared Pro-Gly-Pro tail is the design element both molecules depend on. Proline rich carboxy termini are poor substrates for common exopeptidases, so the extension is described in the literature as slowing degradation of the parent fragment in plasma and in brain tissue. That relative stability is also why both compounds appear in published animal studies using nasal delivery, and why both are offered in a nasal research format alongside lyophilized powder. The nasal format is a solution presentation for research handling, not a change to the molecule itself.
Handling differs in one important respect. The methionine in Semax oxidises readily, so Semax solutions are protected from air, light and warm storage more carefully than Selank solutions, and oxidation typically shows up as a late eluting shoulder on HPLC. Both are supplied lyophilized, held at minus 20 degrees Celsius away from light and moisture, reconstituted gently with the diluent appropriate to the assay, refrigerated at 2 to 8 degrees Celsius once in solution, and aliquoted so that repeated freeze thaw is avoided.
Laboratories choose between them by the pathway under test. Neurotrophic factor expression work uses Semax. Work on GABAergic signaling, enkephalin turnover or immune gene expression uses Selank. What remains unsettled for both is the route from a short, rapidly cleared peptide to the central changes reported, since neither has a confirmed receptor and both are characterised through downstream markers rather than direct binding data.