Semax

Semax is a synthetic melanocortin-derived heptapeptide investigated for its neurotrophin-modulating, neuroprotective, and cognitive-enhancing properties, achieved through BDNF/NGF upregulation and modulation of the monoaminergic system.

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Description

Semax (CAS: 80714-61-0) is a synthetic analogue of the ACTH 4–7 fragment, extended with a C-terminal Pro-Gly-Pro sequence to confer enhanced metabolic stability and CNS bioavailability. Originally developed by the Institute of Molecular Genetics of the Russian Academy of Sciences, Semax has been extensively characterized in preclinical models for its pleiotropic effects on central nervous system function, neuroplasticity, and neuroprotection. Molecular & Pharmacological Profile: At the molecular level, Semax potently upregulates the expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), acting on tropomyosin receptor kinase (Trk) signaling pathways associated with neuronal survival, synaptic plasticity, and long-term potentiation (LTP). It does not bind the melanocortin receptors (MC1R–MC5R) with significant affinity and exhibits no corticotropic activity, distinguishing it pharmacologically from its parent ACTH sequence. Semax has been shown to modulate dopaminergic and serotonergic neurotransmission, influence enkephalinase activity, and exert inhibitory effects on neuroinflammatory cascades, including downregulation of pro-inflammatory cytokine expression (IL-1β, TNF-α) in glial cell populations. Reported effects on cerebrovascular tone suggest additional utility in models of ischemia-reperfusion injury, where it has demonstrated reduction of the penumbral infarct zone and attenuation of oxidative stress markers. Research Areas: Neurotrophic signaling — BDNF/NGF axis modulation, TrkB receptor activation, ERK/MAPK and PI3K/Akt pathway involvement Cognitive function — hippocampal-dependent learning and memory consolidation in rodent behavioral models (Morris water maze, novel object recognition) Neuroprotection — preclinical models of focal cerebral ischemia, hypoxia, and excitotoxic neuronal injury Neuroinflammation — glial activation and cytokine profile modulation in CNS injury models Monoaminergic regulation — dopamine and serotonin turnover in prefrontal and limbic regions Administration & Stability: Semax is typically reconstituted in sterile bacteriostatic saline or PBS for intranasal or subcutaneous delivery in research applications. Intranasal administration facilitates transport via the olfactory epithelium, offering a non-invasive route with documented CNS uptake. The Pro-Gly-Pro C-terminal extension confers resistance to prolyl endopeptidase degradation, extending the peptide's half-life relative to the native ACTH 4–7 core. Lyophilized material should be stored at –20°C and protected from repeated freeze-thaw cycles. Reconstituted solutions are stable at 4°C for short-term use under sterile conditions. Intended Use: For research use only (RUO). Not for human or veterinary use. Not for therapeutic, diagnostic, or clinical application.