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Semax

Met-Glu-His-Phe-Pro-Gly-Pro · ACTH(4-7)PGP

Nootropic & CNSPreclinical
From$1.22/mgCompare prices
MW
813.9g/mol
Formula
C37H51N9O10S

Semax is a synthetic heptapeptide derived from the adrenocorticotropic hormone (ACTH) fragment, specifically the ACTH (4-7) sequence, and is recognized for its neuroprotective and nootropic properties. Researchers primarily study Semax for its potential effects on cognitive function, neuroprotection, and recovery from neurological injuries. Key findings indicate that Semax promotes functional recovery following spinal cord injury by modulating molecular pathways related to neuronal health and reducing oxidative stress, while also demonstrating improvements in cognitive performance and reductions in amyloid plaque formation in models of Alzheimer's disease. Current research status highlights a growing interest in Semax as a therapeutic candidate, although further clinical trials are needed to establish its efficacy and safety in human populations.

Chemical Profile

Chemical Profile

Chemical structure
Chemical Structure
FormulaC37H51N9O10S
Molecular Weight813.9 g/mol
CAS Number80714-61-0
PubChem CID9811102

Half-Life

INIntranasal

~15 minutes

POOral

Poor bioavailability

Intranasal administration is preferred due to rapid absorption and onset of action.

Mechanism

Mechanism of Action

Semax primarily targets the μ-opioid receptor, modulating the ubiquitin-specific protease USP18 to promote deubiquitination processes that enhance neuronal survival and functional recovery after spinal cord injury. It also influences neuroplasticity by enhancing brain-derived neurotrophic factor (BDNF) signaling and exhibits neuroprotective properties by preventing amyloid beta aggregation, particularly in the presence of copper ions, although the complete mechanism remains to be fully elucidated. Additionally, Semax impacts various signaling pathways, including the PI3K/Akt and MAPK pathways, contributing to its effects on cognitive function and neuroprotection.

Research

56 Research Publications

652

Total Citations

4

Human/RCT

1.3

Avg. Influence

2025

Latest

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#01

Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia.

Dmitrieva Veronika G, et al. · Cellular and molecular neurobiology · 2010

AnimalInfluence1.0
52
The study demonstrated that Semax and its C-terminal peptide PGP activate the transcription of neurotrophins and their receptors in rats after cerebral ischemia.

Key findings

  1. 01Semax and PGP both increased the expression of neurotrophins and their receptors in the brains of rats after a stroke.
  2. 02Semax specifically enhanced the production of certain neurotrophins at different time points following the stroke.
  3. 03PGP's effects were less specific compared to Semax, indicating different mechanisms of action.
60 nmol/kg of body weight (BW)intraperitoneal(male adult Sprague-Dawley rats)daily5, 50, 150, and 450 μg/kgintraperitoneal(Wistar male rats)12-15 min before modeling restraint stress1 μMperfusion solution(isolated cerebral neurons)not mentioned0.1 and 1 μMperfusion solution(hippocampal pyramidal neurons)not mentioned0.15 mg/kgintraperitoneal(rodents)not mentioned
PubMed
#02

Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus.

Dolotov Oleg V, et al. · Brain research · 2006

Animal
46
The study demonstrated that Semax increased BDNF and trkB expression in the rat hippocampus, correlating with improved cognitive functions.

Key findings

  1. 01Researchers observed a 1.4-fold increase in BDNF protein levels in the hippocampus after Semax treatment.
  2. 02There was a 1.6-fold increase in trkB protein activation levels following Semax application.
  3. 03Semax-treated rats demonstrated enhanced learning behaviors, indicated by increased conditioned avoidance reactions.
PubMed
#03

Effects of semax and its Pro-Gly-Pro fragment on calcium homeostasis of neurons and their survival under conditions of glutamate toxicity.

In VitroInfluence3.0
35
Researchers observed that Semax and its Pro-Gly-Pro fragment improved neuronal survival and delayed calcium dysregulation under glutamate toxicity in cultured cerebellar granule cells.
60 nmol/kg of body weight (BW)intraperitoneal(male adult Sprague-Dawley rats)daily5, 50, 150, and 450 μg/kgintraperitoneal(Wistar male rats)12-15 min before modeling restraint stress1 μMperfusion solution(isolated cerebral neurons)not mentioned0.1 and 1 μMperfusion solution(hippocampal pyramidal neurons)not mentioned0.15 mg/kgintraperitoneal(rodents)not mentioned
PubMed
#04

The effect of Semax and its C-end peptide PGP on the morphology and proliferative activity of rat brain cells during experimental ischemia: a pilot study.

Animal
30
The study demonstrated that Semax increases the proliferation of neuroglia and endothelial cells in the rat brain during experimental ischemia.
60 nmol/kg of body weight (BW)intraperitoneal(male adult Sprague-Dawley rats)daily5, 50, 150, and 450 μg/kgintraperitoneal(Wistar male rats)12-15 min before modeling restraint stress1 μMperfusion solution(isolated cerebral neurons)not mentioned0.1 and 1 μMperfusion solution(hippocampal pyramidal neurons)not mentioned0.15 mg/kgintraperitoneal(rodents)not mentioned
PubMed
#05

The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis.

Animal
27
The study demonstrated that Semax alters gene expression related to immune and vascular systems in rat brain tissues following focal ischemia.
60 nmol/kg of body weight (BW)intraperitoneal(male adult Sprague-Dawley rats)daily5, 50, 150, and 450 μg/kgintraperitoneal(Wistar male rats)12-15 min before modeling restraint stress1 μMperfusion solution(isolated cerebral neurons)not mentioned0.1 and 1 μMperfusion solution(hippocampal pyramidal neurons)not mentioned0.15 mg/kgintraperitoneal(rodents)not mentioned
PubMed
#06

[A nootropic adrenocorticotropin analog 4-10-semax (l5 years experience in its design and study)].

HumanInfluence1.0
24
The study demonstrated that semax enhances memory and attention in humans under extreme conditions and shows no negative side effects, indicating its potential for broader medical applications.
5, 50, 150, and 450 μg/kgintraperitoneal(Wistar male rats)12-15 min before modeling restraint stress60 nmol/kg of body weight (BW)intraperitoneal(male adult Sprague-Dawley rats)daily6000 mcg/daynot specified(patients after ischemic stroke)2 courses for 10 days with 20 day interval0.05 mg/kgnot specified(mice)single administration75 and 0.1 mg/kg per daynot specified(mice)preventive course administration for 6 days50 and 250 microg/kg bodyweightintranasal(rat)not specified
PubMed
#07

Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats.

Animal
24
Researchers observed that Semax suppressed inflammatory gene expression and activated neurotransmission-related genes in the brains of rats following cerebral ischemia-reperfusion.
60 nmol/kg of body weight (BW)intraperitoneal(male adult Sprague-Dawley rats)daily5, 50, 150, and 450 μg/kgintraperitoneal(Wistar male rats)12-15 min before modeling restraint stress1 μMperfusion solution(isolated cerebral neurons)not mentioned0.1 and 1 μMperfusion solution(hippocampal pyramidal neurons)not mentioned0.15 mg/kgintraperitoneal(rodents)not mentioned
PubMed
#08

Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain.

Animal
23
The study demonstrated that Semax increased BDNF levels in the rat basal forebrain, suggesting a mechanism for its cognitive effects.
60 nmol/kg of body weight (BW)intraperitoneal(male adult Sprague-Dawley rats)daily5, 50, 150, and 450 μg/kgintraperitoneal(Wistar male rats)12-15 min before modeling restraint stress1 μMperfusion solution(isolated cerebral neurons)not mentioned0.1 and 1 μMperfusion solution(hippocampal pyramidal neurons)not mentioned0.15 mg/kgintraperitoneal(rodents)not mentioned
PubMed
#09

Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents.

Eremin Kirill O, et al. · Neurochemical research · 2005

Animal
23
Researchers observed that Semax activated dopaminergic and serotoninergic systems in rodents, enhancing the effects of D-amphetamine on dopamine release.

Key findings

  1. 01Semax significantly increased the levels of a serotonin marker in the brain.
  2. 02The peptide enhanced the effects of D-amphetamine on dopamine levels.
  3. 03Semax also boosted locomotor activity in the rodents when combined with D-amphetamine.
60 nmol/kg of body weight (BW)intraperitoneal(male adult Sprague-Dawley rats)daily5, 50, 150, and 450 μg/kgintraperitoneal(Wistar male rats)12-15 min before modeling restraint stress1 μMperfusion solution(isolated cerebral neurons)not mentioned0.1 and 1 μMperfusion solution(hippocampal pyramidal neurons)not mentioned0.15 mg/kgintraperitoneal(rodents)not mentioned
PubMed
#10

Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action.

Animal
21
Researchers observed multidirectional changes in NGF and BDNF gene expression in the hippocampus, frontal cortex, and retina of rats following Semax administration.
60 nmol/kg of body weight (BW)intraperitoneal(male adult Sprague-Dawley rats)daily5, 50, 150, and 450 μg/kgintraperitoneal(Wistar male rats)12-15 min before modeling restraint stress1 μMperfusion solution(isolated cerebral neurons)not mentioned0.1 and 1 μMperfusion solution(hippocampal pyramidal neurons)not mentioned0.15 mg/kgintraperitoneal(rodents)not mentioned
PubMed
Safety

Safety & Handling

Research Gaps

No randomized controlled human trials have been conducted to assess the efficacy and safety of Semax in various therapeutic contexts, particularly in human populations. Additionally, the long-term effects of Semax administration on cognitive function and neuroprotection remain unclear, as does the detailed mechanism by which Semax modulates the μ-opioid receptor and its downstream effects on ubiquitination and lysosomal stability.

Solubility

Semax is soluble in water and saline solutions.

Storage & Handling

Lyophilized

Stable for 2+ years at -20°C, 12 months at 4°C

Reconstituted

Use within 14 days when refrigerated at 4°C

Avoid

Avoid repeated freeze-thaw cycles, direct light

Solvent

Bacteriostatic water or sterile saline recommended

Safety information is derived from published research and may not reflect all known risks. This is not medical advice.

Legal Status

Legal Status

🇩🇪DE

Not approved as a medicinal product. Not a controlled substance. Sale as research chemical is a legal grey area.

🇺🇸US

Not approved by the FDA. Not scheduled by the DEA.

🇦🇺AU

Data limited

🇬🇧UK

Data limited

Legal status information is provided for general reference only and may not reflect the most current regulatory changes. Always verify with official government sources before making any decisions.

Community Insights

Community Insights

Publications per Year

49 total
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Pricing

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Legal Disclaimer

This page is for informational and research purposes only. All information is based on published scientific literature and does not constitute medical advice, diagnosis, or treatment recommendations. Many substances listed may not be approved for human use and may be subject to drug regulation laws (e.g., AMG in Germany, FDA in the US). PepStack does not encourage the use of any substance on humans. Always consult a qualified healthcare professional before making any health-related decisions. Use of this information is entirely at your own risk. PepStack assumes no liability for the accuracy, completeness, or timeliness of the content provided. Full disclaimer