Semax
Published research and evidence base
Semax is a synthetic heptapeptide, Met-Glu-His-Phe-Pro-Gly-Pro, consisting of the ACTH(4-7) fragment extended with a C-terminal Pro-Gly-Pro tripeptide that confers resistance to enzymatic degradation. It lacks corticotropic activity and is registered in Russia for ischaemic stroke, optic nerve disease and cognitive indications. Its best-characterised actions are regulation of BDNF and NGF expression and broad transcriptomic modulation of inflammatory and neurosignalling genes in rodent cerebral ischaemia models. Human evidence is dominated by Russian clinical studies of stroke and optic neuropathy, with two small placebo-controlled fMRI studies in healthy volunteers; no regulatory-grade Western trial exists.
- Studies cited
- 18
- Published 2023+
- 10
- Newest paper
- 2025
- Last reviewed
- Aug 2026
Recurring themes in the literature
- ACTH(4-10) analogue
- melanocortin
- BDNF and NGF expression
- ischaemic stroke neuroprotection
- transcriptomic modulation
- copper and amyloid interaction
- intranasal nootropic
- default mode network
Compound identifiers
- CAS
- 80714-61-0
- PubChem
- 9811102
Recommended by an FDA advisory committee.
On 23–24 July 2026 the FDA’s Pharmacy Compounding Advisory Committee considered Semax for the 503A Bulks List and recommended its addition on a reported vote of 8–5 with one abstention. Heard on the second day of the meeting and recommended on a divided vote.
This is not an approval. The committee advises; it does not decide. The recommendation is not binding, the FDA has not completed the rulemaking that would formally change anything, and inclusion on the 503A Bulks List is not equivalent to FDA approval of a drug. The list also governs pharmacy compounding for patients, which is a separate activity from research-use-only supply.
What the July 2026 advisory vote actually did sets out the process, the other compounds heard, and the four things the vote is routinely misreported as meaning.
What Semax is, chemically.
- Molecular formula
- C37H51N9O10S
- Molecular weight
- 813.9 g/mol
- CAS number
- 80714-61-0
- PubChem CID
- 9811102
These figures come from the PubChem record for this compound and describe the free base. Lyophilised peptide is normally supplied as an acetate or trifluoroacetate salt and carries residual water, so the mass of powder in a vial is not the same quantity as the molecular weight above would suggest. Chromatographic purity on a certificate of analysis does not resolve that difference either — how to read a certificate of analysis explains why.
18 published studies.
Ordered by strength of study design, then by recency. Every entry links to its source record so the finding can be checked against the paper rather than taken on our word.
- 01Human clinical2020
Functional Connectomic Approach to Studying Selank and Semax Effects
Panikratova YR, et al. · Doklady Biological Sciences · placebo-controlled resting-state fMRI, 52 healthy participants scanned before and 5 and 20 min after Semax, Selank or placebo
Semax and Selank produced distinguishable changes in resting-state functional connectivity between the right amygdala and right temporal cortex relative to placebo.
- 02Human clinical2018
Effects of Semax on the Default Mode Network of the Brain
Lebedeva IS, et al. · Bulletin of Experimental Biology and Medicine · placebo-controlled resting-state fMRI, 24 healthy volunteers aged 43.9 +/- 9.5 years; intranasal 1% Semax (n=14) vs placebo (n=10)
The Semax group showed a greater volume of the rostral (medial frontal cortex) subcomponent of the default mode network than controls, demonstrating a measurable acute central effect after intranasal dosing.
- 03Human clinical2018· Russian (English abstract)
[The efficacy of semax in the tretament of patients at different stages of ischemic stroke]
Gusev EI, Martynov MY, Kostenko EV, Petrova LV, Bobyreva SN · Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · clinical trial, n=110 post-ischaemic-stroke patients stratified into early (89 +/- 9 days) and late (214 +/- 22 days) rehabilitation with and without Semax 6000 mcg/day for two 10-day courses
Semax administration raised plasma BDNF levels irrespective of rehabilitation timing and was associated with faster improvement and better final Barthel index scores. The trial was not placebo-controlled.
- 04Human clinical2007· Russian (English abstract)
[The study of chronic partial denervation and quality of life in patients with motor neuron disease treated with semax]
Serdiuk AV, Levitskii GN, Miasoedov NF, Skvortsova VI · Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · open-label trial, n=27 patients with motor neuron disease; intranasal 1% Semax 12 mg/day in two 10-day courses, serial needle EMG and ALS scales
Semax did not influence the course of chronic partial denervation or clinical ALS ratings, but significantly improved total quality-of-life score via emotional state and motivation, peaking at day 10.
- 05Human clinical2000· Russian (English abstract)
[Evaluation of therapeutic effect of new Russian drug semax in optic nerve disease]
Polunin GS, Nurieva SM, Baiandin DL, Sheremet NL, Andreeva LA · Vestnik oftalmologii · controlled clinical trial in vascular, toxic-allergic and inflammatory optic nerve disease and partial optic atrophy; intranasal drops vs endonasal electrophoresis vs control
Addition of Semax to standard therapy was associated with improved visual acuity, enlarged total visual field, increased electrical sensitivity and conductivity of the optic nerve, and improved colour vision.
- 06Human clinical1997· Russian (English abstract)
[Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]
Gusev EI, Skvortsova VI, Miasoedov NF, Nezavibat'ko VN, Zhuravleva EIu, Vanichkin AV · Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · controlled clinical trial, 30 patients with acute hemispheric ischaemic stroke vs 80 conventionally treated controls; EEG mapping and somatosensory evoked potentials
Adding Semax to intensive therapy was associated with faster regression of general cerebral and focal, especially motor, deficits. Effective daily doses were reported as 12 mg for moderate and 18 mg for severe strokes.
- 07Animal in vivo2025
The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer's Disease
Radchenko AI, et al. · Acta Naturae · transgenic APPswe/PS1dE9/Blg mice; open field, novel object recognition and Barnes maze plus histology
Semax and a derivative improved performance on novel object recognition and Barnes maze tests and reduced the number of amyloid inclusions in cortex and hippocampus.
- 08Animal in vivo2025
Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice
Liu R, et al. · British Journal of Pharmacology · T9-T10 contusion spinal cord injury in female C57BL/6 mice, plus PC12 neuroinflammation model; RNA-seq, network pharmacology and molecular docking
Semax improved functional recovery and inhibited lysosomal-membrane-permeabilisation-related pyroptosis, acting via USP18 regulation; docking and pharmacology analyses identified the mu-opioid receptor as a candidate target. This is one of the few non-Russian primary Semax studies.
- 09Animal in vivo2025
Genes That Associated with Action of ACTH-like Peptides with Neuroprotective Potential in Rat Brain Regions with Different Degrees of Ischemic Damage
Filippenkov IB, et al. · International Journal of Molecular Sciences · rat transient middle cerebral artery occlusion (tMCAO), RNA-seq of striatum and frontal cortex at 24 h
Semax and ACTH(6-9)PGP normalised ischaemia-disrupted expression profiles for hundreds of genes in the striatum, with fewer differentially expressed genes than in the frontal cortex, indicating region-dependent transcriptomic effects.
- 10Animal in vivo2024
ACTH-like Peptides Compensate Rat Brain Gene Expression Profile Disrupted by Ischemia a Day After Experimental Stroke
Filippenkov IB, et al. · Biomedicines · rat tMCAO model, whole-transcriptome sequencing of frontal cortex 24 h post-stroke
ACTH-like peptides including Semax partially compensated ischaemia-induced disturbance of the brain gene expression profile at 24 h, affecting neurotransmitter and inflammatory gene sets.
- 11Animal in vivo2024
Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress
Inozemtseva LS, et al. · European Journal of Pharmacology · male Sprague-Dawley rats, chronic unpredictable stress; daily intraperitoneal Semax or Melanotan II at 60 nmol/kg
Semax reversed or attenuated stress-induced anhedonia, suppression of body-weight gain, adrenal hypertrophy and reduced hippocampal BDNF. No effect was seen on forced swim test immobility.
- 12Animal in vivo2024
Changes of Transcriptomic Activity in Rat Brain Cells under the Influence of Synthetic Adrenocorticotropic Hormone-Like Peptides
Filippenkov IB, et al. · Biochemistry (Moscow) · rat brain cells, transcriptomic profiling under ACTH-like peptide administration
Synthetic ACTH-like peptides including Semax produced measurable shifts in brain cell transcriptomic activity, extending the group's stroke-model transcriptomics to non-ischaemic conditions.
- 13Animal in vivo2023
Synthetic Adrenocorticotropic Peptides Modulate the Expression Pattern of Immune Genes in Rat Brain following the Early Post-Stroke Period
Filippenkov IB, et al. · Genes · rat tMCAO model, RNA-seq of dorsolateral frontal cortex 4.5 h after occlusion
Semax was associated with 131 differentially expressed genes and ACTH(6-9)PGP with 322 at 4.5 h post-stroke; both partially prevented ischaemia-induced changes in immune- and neurosignalling-related expression profiles.
- 14Animal in vivo2010
Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action
Shadrina M, et al. · Journal of Molecular Neuroscience · rat hippocampus, frontal cortex and retina; time-course of NGF and BDNF gene expression after Semax
Semax produced region- and time-dependent changes in NGF and BDNF gene expression, establishing the neurotrophin-induction mechanism most often cited for the compound.
- 15In vitro2025
The Effect of Peptide Semax, an ACTH(4-10) Analogue, on Intracellular Calcium Dynamics in Rat Brain Neurons
Kolbaev SN, et al. · Bulletin of Experimental Biology and Medicine · rat hippocampal and cerebellar slices, calcium imaging; Semax 1 microM
Semax increased the frequency of spontaneous intracellular calcium fluctuations in CA1 pyramidal-layer cells but did not affect proton-stimulated calcium entry in cerebellar granule cells, arguing against acid-sensing ion channels as the primary neuroprotective mechanism.
- 16In vitro2025
Semax, a Copper Chelator Peptide, Decreases the Cu(II)-Catalyzed ROS Production and Cytotoxicity of aβ by Metal Ion Stripping and Redox Silencing
Tomasello MF, et al. · Bioinorganic Chemistry and Applications · cell-free and cell-based assays of Cu(II)-amyloid beta redox chemistry and cytotoxicity
Semax stripped Cu(II) from amyloid beta and silenced its redox activity, reducing catalysed reactive oxygen species production and associated cytotoxicity in vitro.
- 17In vitro2023
Synthetic corticotropins and the GABA-receptor system: Direct and delayed effects
Vyunova TV, et al. · Chemical Biology & Drug Design · isolated rat brain plasma membranes plus systemic administration in an acute restraint stress rat model; [3H]GABA binding
Semax and related synthetic corticotropins each altered [3H]GABA binding differently at high- and low-affinity sites. Acute restraint stress reduced binding at the low-affinity site, and peptide pre-administration did not prevent this stress effect.
- 18In vitro2022
Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models
Sciacca MFM, et al. · ACS Chemical Neuroscience · artificial membrane models of copper-induced amyloid beta aggregation
Semax modified copper-induced amyloid beta aggregation and amyloid formation at model membranes, supporting a metal-coordination component to its reported neuroprotective chemistry.
What this evidence does not establish.
Russian marketing authorisation was granted on the basis of domestic trials that were largely open-label or actively controlled rather than double-blind and placebo-controlled; no Semax trial has been registered or completed under EMA or FDA standards. Effects on cognition in healthy adults are supported only by two small fMRI studies with surrogate imaging endpoints, and no dose-ranging, pharmacokinetic or long-term safety data are available in Western populations.
Common questions about the research.
- What is Semax?
Semax is a synthetic heptapeptide made from the ACTH(4-7) fragment extended with Pro-Gly-Pro. It was developed in Russia in the 1980s and is studied primarily in neurotrophic-signalling and cerebral-ischaemia research. It carries none of the hormonal corticotropic activity of full-length ACTH.
- What does the research literature actually describe?
Rodent studies report increases in brain-derived neurotrophic factor protein and changes in BDNF and trkB expression, plus broad transcriptome shifts in ischaemia-reperfusion models. A Russian clinical literature examines intranasal courses in ischaemic stroke. These are research findings in defined study settings, not established outcomes, and nothing here is a claim about what the compound does for a person.
- How does Semax differ from Selank?
Both share the Pro-Gly-Pro stabilising tail and both came out of the same Russian research programme, but their active fragments differ. Semax derives from ACTH(4-7) and is studied in neurotrophic and ischaemia models; Selank derives from the immune tetrapeptide tuftsin and is studied in anxiety and stress models.
Available from our catalog
For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice, and no study summarised here should be read as a recommendation.