Semax: Complete Research Profile & Neuroprotection Data
ACTH(4-10)-Pro-Gly-ProSemax heptapeptide
Semax is a synthetic heptapeptide corresponding to the ACTH(4-10) fragment with a stabilizing Pro-Gly-Pro extension at the C-terminus. This modification provides resistance to enzymatic degradation while retaining the neurotrophic properties of the ACTH(4-10) sequence. A key design feature is the elimination of steroidogenic activity — unlike the parent ACTH molecule, Semax does not stimulate cortisol or other adrenal hormone production. This makes it suitable for studying neurotrophic and neuroprotective mechanisms independent of the hypothalamic-pituitary-adrenal (HPA) axis. Semax has been approved as a neuroprotective medication in Russia and is studied globally for cognitive enhancement, stroke recovery, and neurodegenerative disease research.
Technical Specifications
CAS Number
80714-61-0
Molecular Formula
C37H51N9O10S
Molecular Weight
813.93 g/mol
Amino Acids
7
Sequence
Met-Glu-His-Phe-Pro-Gly-Pro
Purity
≥99% (HPLC)
Appearance
White lyophilized powder
Salt Form
Acetate
Solubility
Soluble in water
Storage
-20°C lyophilized, 2-8°C reconstituted
Origin & Discovery
Semax is a synthetic analog of ACTH(4-10), the biologically active fragment of Adrenocorticotropic Hormone. It was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences with a Pro-Gly-Pro C-terminal extension for enhanced metabolic stability. Unlike full-length ACTH, Semax does not stimulate cortisol production.
Mechanism of Action
Semax engages neurotrophic signaling pathways that are fundamental to neuronal survival, plasticity, and cognitive function.
BDNF/TrkB Upregulation: Semax significantly upregulates Brain-Derived Neurotrophic Factor (BDNF) expression and its receptor TrkB (Tropomyosin receptor kinase B). The BDNF/TrkB signaling cascade promotes neuronal survival, synaptic plasticity, and long-term potentiation — the molecular basis of learning and memory.
NGF Modulation: Semax modulates Nerve Growth Factor (NGF) expression, another critical neurotrophin involved in the growth, maintenance, and survival of neurons, particularly cholinergic neurons in the basal forebrain that are central to memory function.
Melanocortin Receptor Signaling: As an ACTH fragment, Semax interacts with melanocortin receptors (MC3R and MC4R), which are expressed throughout the central nervous system and are involved in attention, learning, memory retrieval, and neuroprotection.
No Cortisol Effects: A critical distinction from ACTH is that Semax does not bind MC2R (the primary receptor mediating cortisol release). This means Semax provides neurotrophic stimulation without activating the stress hormone axis.
Neuroprotection & Stroke Research
Semax has been studied in the context of neuroprotection against ischemic injury. Dolotov et al. (2006) demonstrated that Semax protected neurons from oxidative stress-induced damage through upregulation of BDNF and activation of survival signaling cascades. Gusev et al. (1997) published data on Semax's neuroprotective effects in stroke models, showing reduced infarct volume and improved neurological outcomes in rodents treated with the peptide following induced cerebral ischemia. These findings supported clinical investigations in Russia where Semax has been used in acute stroke management protocols.
Citations
Dolotov OV, et al. (2006) "Semax neuroprotection via BDNF upregulation."
Gusev EI, et al. (1997) "Semax in stroke models and neuroprotection."
Cognitive Enhancement
The cognitive-enhancing properties of Semax have been documented across multiple behavioral paradigms. Eremin et al. (2005) demonstrated that Semax enhanced memory consolidation and retrieval in passive avoidance and water maze tasks, with effects persisting beyond the treatment period. Agapova et al. (2007) characterized Semax's effects on gene expression in the brain, identifying upregulation of genes involved in synaptic plasticity, neurotransmitter synthesis, and ion channel regulation. The pattern of gene expression changes suggests that Semax promotes a state of enhanced neural plasticity rather than simply increasing neurotransmitter levels.
Citations
Eremin KO, et al. (2005) "Semax enhances memory consolidation and retrieval."
Agapova TY, et al. (2007) "Semax gene expression in brain regions."
Frequently Asked Questions
What is Semax?▼
Semax is a synthetic 7-amino-acid peptide analog of ACTH(4-10), developed at the Russian Academy of Sciences. It retains neurotrophic properties of the ACTH fragment while eliminating cortisol-stimulating activity. It is studied for neuroprotection and cognitive enhancement.
Does Semax affect cortisol levels?▼
No. Unlike full-length ACTH, Semax does not bind the MC2 receptor responsible for adrenal cortisol release. It retains melanocortin receptor activity (MC3R/MC4R) for neurotrophic effects without stimulating the stress hormone axis.