ACTH(4-7) Pro-Gly-Pro — Synthetic heptapeptide engineered for CNS stability and neurotrophic activity. Studied for BDNF upregulation, neuroprotection and monoaminergic modulation in preclinical models.
Semax is a heptapeptide derived from the ACTH(4-10) fragment, stabilised by the Pro-Gly-Pro C-terminal extension that confers resistance to enzymatic degradation. Unlike the parent ACTH fragment, Semax lacks melanocortin receptor-mediated adrenocortical activity while retaining and amplifying CNS-relevant signalling pathways.
The Met-Glu-His-Phe core (ACTH 4-7) binds with low affinity to melanocortin receptors (MC4R, MC5R). This partial agonism triggers intracellular cAMP elevation in hypothalamic and limbic circuits without activating adrenocortical steroidogenesis.
Downstream cAMP → PKA → CREB phosphorylation drives transcription of Bdnf gene (exon IV promoter). Quantitative RT-PCR studies in rat hippocampus report 1.4–2.1× increases in BDNF mRNA within 2–6 hours of administration.
Concurrent upregulation of Nerve Growth Factor (NGF) and Neurotrophin-3 (NT-3) contributes to broader neurotrophic support of cholinergic basal forebrain neurons — a circuit implicated in attention and memory consolidation.
The C-terminal Pro-Gly-Pro tripeptide (PGP) independently interacts with enkephalin-degrading enzymes, increasing endogenous enkephalin bioavailability. This secondary mechanism contributes to Semax's observed analgesic and anxiolytic effects in rodent models.
Semax downregulates NF-κB–driven expression of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) in activated microglia. Gene array studies following middle cerebral artery occlusion (MCAO) in rats identified 84 immune-related genes significantly modulated within 24h.
Multiple rodent studies using the Morris water maze and radial arm maze paradigms demonstrate that Semax administration improves spatial learning acquisition and memory retrieval. Proposed mechanisms include hippocampal BDNF elevation and enhanced cholinergic tone. Effects are dose-dependent, with reversal observed at supra-physiological doses in some models.
Refs: Dolotov OV et al., J Neurochem (2006); Agapova TY et al., Behav Brain Res (2007)
In MCAO ischaemia models, intranasal Semax administered within 1–4h of occlusion reduces cortical infarct volume by 30–55% and attenuates neurological deficit scores. The neuroprotective window appears broader than tPA's, with gene expression analysis showing rapid induction of growth factor genes and suppression of inflammatory cascades within 3h.
Refs: Isaeva EV et al., Neurochemical Research (2012); Kaplan AY et al., Brain Research (2005)
In elevated plus-maze and forced swim tests, Semax exhibits anxiolytic-like and antidepressant-like profiles in rodents. Dopamine D2/D3 and serotonin 5-HT2A receptor expression in limbic regions is altered following repeated administration, suggesting a mechanism distinct from classical anxiolytics.
Refs: Levitskaya NG et al., Neuropeptides (2004); Eremin KO et al., Neurochem Int (2005)
Russian clinical investigations (Semax is an approved pharmaceutical in Russia and Ukraine) have explored Semax in optic nerve atrophy and glaucomatous neurodegeneration, reporting improvements in visual field sensitivity and electrophysiological parameters. These studies inform hypothesis generation for further controlled trial design.
Refs: Neroev VV et al., Bull Exp Biol Med (2008)
Each batch of Semax is independently tested by a third-party ISO-accredited laboratory prior to release. The analysis below reflects Batch AV-2025-SMX-056, tested 10 March 2025.
| Test Parameter | Method | Specification | Result | Status |
|---|---|---|---|---|
| Identity (sequence) | ESI-MS / MS-MS fragmentation | Matches theoretical m/z | Confirmed (MH⁺ 888.0 Da) | PASS |
| Purity (HPLC) | RP-HPLC C18, 210nm | ≥98.0% | 99.3% | PASS |
| Water content | Karl Fischer titration | ≤8.0% | 5.8% | PASS |
| Appearance | Visual inspection | White lyophilised powder | Conforms | PASS |
| Heavy metals (ICP-MS) | ICP-MS (EPA 200.8) | ≤10 ppm total | <2 ppm | PASS |
| Bacterial endotoxins | LAL chromogenic assay | ≤10 EU/mg | <1 EU/mg | PASS |
| Form | Temperature | Duration | Container |
|---|---|---|---|
| Lyophilised powder | −20°C (preferred) or 2–8°C | 24 months (−20°C) 12 months (2–8°C) | Sealed amber vial, argon-purged |
| Reconstituted solution (saline) | 2–8°C | ≤7 days | Sterile vial, light-protected |
| Reconstituted (BAC water) | 2–8°C | ≤28 days | Sterile vial, light-protected |
Semax is more susceptible to oxidation at the methionine residue than most synthetic peptides. Protect from light, avoid dissolved oxygen, and do not store in plastic syringes long-term.
Work under laminar flow or in a clean environment. Wipe vial septa with 70% IPA and allow to dry before penetration.
Use sterile bacteriostatic water (0.9% benzyl alcohol) for extended stability (≤28d). Sterile 0.9% sodium chloride is also compatible for immediate-use preparations.
For a 1 mg vial, add 1 mL solvent → 1000 mcg/mL stock. Inject slowly along the inner vial wall. Do not inject directly onto the lyophilised cake.
Gently swirl (do not vortex or shake). Semax is highly water-soluble; clear dissolution typically occurs within 60 seconds.
Wrap vial in foil immediately after reconstitution. Store at 2–8°C. Due to Met oxidation risk, consume within 7 days for aqueous/saline preparations or 28 days with BAC water.
Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide analogue of the ACTH(4-7) fragment. The full ACTH molecule (39 amino acids) acts on pituitary-adrenal axis receptors to stimulate cortisol release. The ACTH(4-7) fragment retains behavioural and neuroprotective properties without adrenocortical activity. Semax's C-terminal Pro-Gly-Pro extension further stabilises the peptide against enzymatic degradation, dramatically extending functional activity despite a short plasma half-life.
While plasma half-life is very short (2–7 minutes), the downstream gene expression changes induced by Semax persist considerably longer. BDNF mRNA upregulation has been documented for up to 24 hours in hippocampal tissue following a single administration in rodents. Some studies report sustained neurotrophic effects for several days following repeated dosing. This dissociation between pharmacokinetics and pharmacodynamics is a defining feature of neurotrophic peptides.
No. Semax and Selank are distinct compounds developed by the Institute of Molecular Genetics (Russian Academy of Sciences) in the same research programme. Selank is a heptapeptide analogue of the endogenous immunomodulatory peptide tuftsin (Thr-Lys-Pro-Arg), with a Pro-Gly-Pro C-terminal extension similar to Semax. Both exhibit anxiolytic and nootropic profiles in rodent models, but their receptor targets and primary mechanisms differ. Selank is more strongly associated with GABAergic modulation and cytokine regulation; Semax with BDNF upregulation and monoamine modulation.
Semax is highly water-soluble. For typical research concentrations, reconstitute 1 mg in 1 mL bacteriostatic water to yield a 1 mg/mL (1000 mcg/mL) stock solution. This can be further diluted with sterile saline to working concentrations. For intranasal delivery studies, ensure the final vehicle is isotonic to minimise mucosal irritation in animal models.
Semax has been studied in human subjects within the Russian regulatory framework, where it holds pharmaceutical registration (approved drug status). Russian clinical trials have investigated its use in acute ischaemic stroke, optic nerve atrophy, and cognitive rehabilitation. However, these trials generally lack the double-blind, placebo-controlled, GCP-compliant design required for regulatory approval in the EU or USA. Semax is not approved by the EMA or FDA and is not authorised for therapeutic use in these jurisdictions. AVREA supplies Semax exclusively for preclinical research purposes.
Among synthetic peptides that upregulate BDNF, Semax is distinguished by its specificity and the breadth of its neurotrophic profile (BDNF + NGF + NT-3 co-upregulation). It lacks the glucocorticoid-mediated BDNF suppression that complicates stress hormone interactions. Compared to exercise-induced BDNF release (which is transient and exercise-dose-dependent), Semax produces more sustained hippocampal BDNF gene expression changes in controlled preclinical settings. Dihexa (N-hexanoic-Tyr-Ile-Ahx-Pro) is another research peptide linked to BDNF signalling via HGF/c-Met but operates via a mechanistically distinct pathway.
Independently verified by third-party ISO-accredited laboratory. COA available on request. For qualified research institutions only.
View Semax in Store → Reconstitution Protocol Guide