Semax Peptide for In Vitro Research: A Synthetic Neuroprotective Derivative of ACTH with Cognitive and Neuroregenerative Properties

CAS Number: 80714-61-0

Overview

Semax is a synthetic heptapeptide derived from the adrenocorticotropic hormone (ACTH 4-10) fragment, developed in Russia for its neuroprotective, nootropic, and cerebrovascular-modulating effects. It has been extensively studied in models of neurodegeneration, ischemia, inflammation, and cognitive decline, and is widely utilized in neuroscience research for exploring neurotrophin regulation, synaptic plasticity, and oxidative stress mechanisms.

Semax is particularly notable for its unique ability to modulate neurotrophic factor expression (especially BDNF) and inhibit the breakdown of enkephalins and other regulatory peptides, with no hormonal activity despite its ACTH origin.

Chemical and Structural Information

• Synonyms: Met-Glu-His-Phe-Pro-Gly-Pro
• Molecular Formula: C37H51N9O10
• Molecular Weight: 811.87 g/mol
• Amino Acid Sequence: Met-Glu-His-Phe-Pro-Gly-Pro
• Chemical Modifications: C-terminal amidation; incorporates the core fragment of ACTH (4-10) with added Pro-Gly-Pro for enhanced enzymatic stability and prolonged biological activity.
• CAS Number: 80714-61-0
• Peptide Class: Synthetic neuropeptide (ACTH fragment analog)

Mechanism of Action

Semax exerts its effects through a variety of neurobiological mechanisms:

• Neurotrophin Upregulation: Significantly increases brain-derived neurotrophic factor (BDNF) and NGF expression in neurons and glial cells.
• NMDA and AMPA Modulation: Affects glutamatergic transmission and calcium homeostasis, promoting neuronal survival and plasticity.
• Antioxidant and Anti-inflammatory Effects: Reduces reactive oxygen species (ROS), lipid peroxidation, and pro-inflammatory cytokines (e.g., TNF-α, IL-1β) in cellular models.
• Enkephalinase Inhibition: Prevents degradation of endogenous enkephalins and other neuropeptides, enhancing analgesic and adaptive responses.
• No Corticotropic Activity: Despite being ACTH-derived, Semax does not activate melanocortin 2 receptors (MC2R) or induce corticosteroid release, making it hormonally inert.

Research Applications

1. Neuroprotection and Ischemia Models

• Preserves neuronal structure and function in models of cerebral ischemia and stroke.
• Enhances mitochondrial stability and energy metabolism under hypoxic conditions.
• Demonstrates anti-apoptotic effects via regulation of Bcl-2 and caspase activity.

2. Cognitive and Synaptic Plasticity Studies

• Improves learning and memory in hippocampal cell culture and rodent models.
• Elevates long-term potentiation (LTP) and dendritic spine density.
• Used to study the relationship between BDNF expression and cognitive resilience.

3. Inflammation and Oxidative Stress Modulation

• Inhibits pro-inflammatory signaling in glial cell and microglia cultures.
• Reduces oxidative damage in aging and neurodegenerative models.
• Supports neurovascular protection and blood-brain barrier integrity.

4. Enkephalinergic and Pain Pathways

• Investigated in models of neuropathic pain, where it enhances endogenous opioid tone via enkephalin preservation.
• Modulates stress and adaptive responses through limbic system signaling.

Future Research Directions

• Exploration of Semax analogs (e.g., N-Acetyl Semax, Semax Amidate) for increased blood-brain barrier penetration and receptor selectivity.
• Evaluation in Parkinson’s, Alzheimer’s, and ALS in vitro models.
• Investigation into transdermal and nanoparticle delivery platforms for localized CNS targeting.
• Multi-omic studies to elucidate its gene expression modulation profile, particularly in synaptic and inflammatory gene networks.

References

1. Ashmarin, I.P. et al. (1997). Peptide Semax: stability and biological effects. Neuroscience and Behavioral Physiology, 27(5), 545–549. https://pubmed.ncbi.nlm.nih.gov/9262082
2. Myasoedov, N.F. et al. (2002). Neuroprotective effects of Semax in models of cerebral ischemia. Bulletin of Experimental Biology and Medicine, 133(1), 76–79. https://pubmed.ncbi.nlm.nih.gov/12462989
3. Andreeva, L.A. et al. (2010). Semax modulates the expression of genes involved in inflammation and neuroprotection. Molecular Biology Reports, 37(7), 3085–3091. https://pubmed.ncbi.nlm.nih.gov/19943116
4. Yakovlev, O.A. et al. (2016). Semax stimulates BDNF expression and enhances learning performance. Doklady Biochemistry and Biophysics, 469(1), 250–253. https://pubmed.ncbi.nlm.nih.gov/27496054

Product Specifications

• Form: Lyophilized powder
• Purity: ≥ 98% (HPLC)
• Solubility: Water-soluble; recommended reconstitution in sterile water or buffer (pH 5.5–7.4)
• Storage: -20°C; protect from light and moisture
• Shelf Life: 24 months when properly stored

Disclaimer

This product is intended for research purposes only. It is not approved for human or veterinary use, nor is it intended for clinical, diagnostic, or therapeutic applications. All research must comply with applicable local laws and institutional guidelines. Misuse of this compound for human consumption is strictly prohibited.