Comparison. Research use only.
Semax vs Selank
The two most-studied Russian-developed research peptides, frequently grouped together and rarely distinguished. Semax is an ACTH(4-7) fragment extended with Pro-Gly-Pro, studied mainly in neurotrophin expression and ischemia models. Selank is a tuftsin-derived heptapeptide investigated as a GABAergic modulator and enkephalinase inhibitor. Overlapping research framing, unrelated mechanisms.
Semax
Semax is a synthetic melanocortin derivative: the ACTH(4-7) fragment with the tripeptide Pro-Gly-Pro added at the C-terminus. That extension is generally described as making the peptide more resistant to enzymatic degradation than the unmodified ACTH fragment. Radioligand studies using tritium-labelled Semax identified specific, reversible, calcium-dependent binding sites in rat basal forebrain membranes, with a dissociation constant of 2.4 nM. That indicates a defined binding target, although the receptor itself has not been definitively identified. A principal downstream correlate is modulation of neurotrophin signalling, the growth-factor signals that support neurons. Semax induces rapid, region-specific changes in Bdnf and Ngf transcription in rat hippocampus, brainstem and cerebellum. In rodent cerebral ischemia models it activates transcription of neurotrophins and their Trk receptors selectively in ischemic cortex, whereas the effect of the Pro-Gly-Pro fragment alone is largely non-specific. Genome-wide transcriptional analysis after permanent middle cerebral artery occlusion shows that the dominant Semax-responsive gene set relates to the immune response, making up over half of the differentially expressed genes at 24 hours. There are additional effects on genes governing endothelial migration and vasculogenesis. At the protein level in a transient occlusion model, Semax was associated with upregulation of active CREB in ischemic subcortical tissue and downregulation of MMP-9, c-Fos and active JNK in adjacent cortex. The mechanistic picture is therefore best described as broad transcriptional modulation of neurotrophic, inflammatory and vascular gene programs, rather than a single defined receptor-effector pathway.
Selank
Selank is a synthetic heptapeptide analogue of tuftsin, a naturally occurring immune-signalling tetrapeptide, extended at the C-terminus with Pro-Gly-Pro. Two mechanistic lines dominate the literature. The first concerns the enkephalinergic system, the body's own opioid-like signalling peptides. Selank inhibits enzymatic breakdown of plasma enkephalin in a dose-dependent way, with a reported half-maximal inhibitory concentration of 15 micromolar, and it was more potent in the same assay than the peptidase inhibitors bacitracin and puromycin. The authors proposed that stabilizing endogenous enkephalins underlies the profile they observed. The second line concerns GABAergic modulation. Radioligand-receptor analysis indicated that Selank affects GABA binding as a positive allosteric modulator, meaning it tunes the receptor rather than switching it on directly, in a subtype-selective and concentration-dependent way. The same work found that its joint action with benzodiazepines is non-cumulative and differs from either agent alone, which suggests binding sites that are distinct but possibly partially overlapping. Expression studies in rat frontal cortex found that Selank altered the expression of a large fraction of an 84-gene neurotransmission panel, and those changes correlated positively with the changes produced by GABA itself. Notably, the corresponding in vitro experiment in IMR-32 neuroblastoma cells found no direct effect of Selank on GABAergic gene transcript levels. Co-administration with GABA suppressed GABA-induced expression changes, which the authors read as modulation of the GABA-receptor interaction rather than direct action on transcription. Selank has additionally been reported to influence Th1/Th2 cytokine balance and interleukin gene expression, consistent with its derivation from an immunopeptide. The mechanism should be regarded as incompletely characterized, and independent reviewers outside Russia have explicitly described the compound as poorly studied.
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