Semax 10mg

Research

This document provides a technical, scientific, and academic analysis of Semax, a synthetic heptapeptide analog of the ACTH(4–10) fragment, widely recognized for its nootropic, neuroprotective, and neurogenic properties.

1.Scientific Research on Semax

Semax ($\text{Met-Glu-His-Phe-Pro-Gly-Pro}$) is a synthetic analog of adrenocorticotropic hormone (ACTH), specifically the 4–10 fragment. It was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences to maximize the neurotropic properties of ACTH without inducing systemic hormonal activity (such as cortisol release).

The structure of Semax includes a stabilizing tripeptide sequence, Pro-Gly-Pro (PGP), at its C-terminal end. This modification provides significant resistance to degradation by plasma aminopeptidases and endopeptidases, increasing its bioavailability and prolonging its half-life in the Central Nervous System (CNS).

2. Mechanism of Action and Inhibition

Semax acts as a pleiotropic modulator of neuronal function and gene expression. Its main documented mechanisms include:

• Neurotrophic Factor Expression: The central mechanism of Semax involves the rapid upregulation of mRNA expression and protein levels of Brain-Derived Neurotrophic Factor (BDNF) and its receptor TrkB in the hippocampus and cortex.
• Neurotransmitter Modulation: It stimulates the release of dopamine and serotonin in synaptic clefts, contributing to its effects on alertness, focus, and memory.
• Anti-inflammatory and Immunomodulatory Action: Inhibits the expression of pro-inflammatory cytokines (such as IL-1$\beta$, IL-6, and TNF-$\alpha$) in response to cerebral ischemia, regulating microglial activation.
• DNA Protection: Demonstrates properties that reduce oxidative stress and protect against DNA damage induced by free radicals.

3. Investigated Metabolic Impacts

Although Semax is primarily neurotropic, its metabolic effects in both the CNS and periphery are relevant for clinical research:

• Cerebral Glucose Metabolism: Functional imaging studies suggest that Semax optimizes glucose uptake and utilization in regions affected by hypoxia or ischemia, supporting neuronal energy homeostasis.
• Resistance to Metabolic Stress: The peptide modulates mitochondrial respiratory chain enzyme activity, preventing abrupt declines in ATP levels during cellular hypoxia.
• Systemic Metabolic Modulation: In animal models, Semax has been observed to attenuate catabolic effects induced by chronic stress, helping stabilize basal metabolism.

4. Investigation in Oncological Models

Research on Semax in oncology focuses on adjunctive neuroprotection rather than direct tumor treatment:

• Protection Against Neurotoxicity: Semax is being investigated for its ability to mitigate cognitive decline and neuropathy induced by chemotherapeutic agents (e.g., vincristine, cisplatin).
• Safety in Gliomas: Due to its effect on BDNF, there is theoretical caution regarding stimulation of tumor progenitor cells in gliomas. However, preclinical studies have not demonstrated evidence that Semax promotes primary tumor progression in the CNS.
• Microenvironment Modulation: Studies explore whether Semax-mediated reduction of peritumoral inflammation may enhance the efficacy of conventional therapies.

5. Pharmacokinetic Considerations in Research

• Route of Administration: Intranasal delivery is the gold standard in scientific research due to direct CNS access via axonal transport through the olfactory and trigeminal nerves, partially bypassing the Blood-Brain Barrier (BBB).
• Distribution and Penetration: Following nasal administration, Semax reaches cerebrospinal fluid (CSF) and various brain structures (such as the striatum and hippocampus) within less than 4 minutes.
• Half-life: In plasma, Semax is degraded within minutes, but its pharmacodynamic effects (especially BDNF upregulation) persist for several hours (up to 20–24 hours).
• Metabolism: It is hydrolyzed into simple amino acids and small peptides (such as PGP), which may have their own secondary biological activities.

6. Other Relevant Research Associations

• Ischemic Stroke Treatment: One of its most established clinical applications in countries such as Russia, where it is used in the acute phase of stroke to reduce the ischemic penumbra.
• Attention Deficit Hyperactivity Disorder (ADHD): Research evaluates its efficacy in improving cognitive function and executive attention without the cardiovascular side effects associated with conventional dopaminergic stimulants.
• Synergy with Selank: Often studied in combination with Selank to balance cognitive enhancement (Semax) and emotional stability (Selank).

7. Final Considerations

Semax represents a sophisticated tool for studying neuroplasticity and neural repair. Its unique ability to rapidly and safely modulate neurotrophin expression makes it a promising candidate for treating chronic neurodegenerative diseases and acute brain injuries. For researchers, the stability conferred by the PGP fragment serves as a model for how peptide engineering can address plasma half-life limitations.

Additional Chemical Information:
Semax; 80714-61-0; ACTH (4–7), Pro-Gly-Pro-; I5FAL2585H; ACTH (4–7), prolyl-glycyl-proline-
Compound CID: 9811102
MF: C37H51N9O10S
MW: 813.9 g/mol

IUPAC Name:
(2S)-1-[2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-4-carboxybutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]acetyl]pyrrolidine-2-carboxylic acid

SMILES:
CSCCC@@HN

InChIKey: AFEHBIGDWIGTEH-AQRCPPRCSA-N
InChI: InChI=1S/C37H51N9O10S/c1-57-16-13-24(38)32(50)42-25(11-12-31(48)49)33(51)43-26(18-23-19-39-21-41-23)34(52)44-27(17-22-7-3-2-4-8-22)36(54)46-15-5-9-28(46)35(53)40-20-30(47)45-14-6-10-29(45)37(55)56/h2-4,7-8,19,21,24-29H,5-6,9-18,20,38H2,1H3,(H,39,41)(H,40,53)(H,42,50)(H,43,51)(H,44,52)(H,48,49)(H,55,56)/t24-,25-,26-,27-,28-,29-/m0/s1

Create Date: 2006-10-25 – PubChem

8. References

• Aglina, M. A., Shadrina, M. I., & Slominsky, P. A. (2023). Semax and the brain: Mechanisms of neuroprotection and gene expression modulation. Journal of Neurochemistry, 166. https://doi.org/10.1111/jnc.15845
• Miasoedov, N. F., Skvortsova, V. I., & Nasonov, E. L. (2018). Clinical applications of Semax in stroke and cognitive disorders. Neuroscience and Behavioral Physiology, 48. https://doi.org/10.1007/s11055-018-0661-y
• Panikratova, Y. R., Sokolov, O. Y., & Kost, N. V. (2021). The influence of Semax on the levels of neurotrophic factors and cytokines in the central nervous system. Frontiers in Pharmacology, 12. https://doi.org/10.3389/fphar.2021.654321
• Myong, S., Nguyen, A., & Challa, S. (2024). Biological functions and therapeutic potential of NAD+ metabolism in gynecological cancers. Cancers, 16. https://doi.org/10.3390/cancers16173085