Data edition of
Residue An evidence-graded reference for peptide science

Monograph in Regulatory peptides

Semax

A synthetic analog of an ACTH fragment, used in Russia for stroke. Its human evidence comes from small, mostly non-randomized Russian clinical studies.

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

C

Best evidence: Limited / early human data

Small clinical studies in stroke published in Russian journals, without large randomized controlled trials; mechanism work is in rats.

Not FDA-approved · FDA compounding nomination withdrawn

Residue Editorial Team · updated

What is Semax?

Semax is a synthetic heptapeptide made of the ACTH(4-7) fragment plus the tripeptide Pro-Gly-Pro1PubMedSemax, an analog of ACTH((4-7)), regulates expression of immune response genes during ischemic brain injury in rats. Medvedeva EV et al. Mol Genet Genomics. 2017.. Russian clinical studies in ischemic stroke report faster functional recovery and higher BDNF levels with semax added to treatment2PubMed[The efficacy of semax in the tretament of patients at different stages of ischemic stroke]. Gusev EI et al. Zh Nevrol Psikhiatr Im S S Korsakova. 2018.,3PubMed[Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]. Gusev EI et al. Zh Nevrol Psikhiatr Im S S Korsakova. 1997.; rat studies link it to immune and vascular gene expression after brain ischemia4PubMedThe peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. Medvedeva EV et al. BMC Genomics. 2014.. It is not FDA-approved, and ClinicalTrials.gov lists no registered study5TrialClinicalTrials.gov registry search: semax. 0 registered studies at fetch..

PubMed records
20911 reviews
Trial publications
41 tagged RCT
Registered studies
00 active · 0 phase 3
Molecular weight
813.9g/mol · PubChem
Evidence grade
CLimited / early human data

Key findings

  1. Semax consists of ACTH(4-7) linked to Pro-Gly-Pro (sequence Met-Glu-His-Phe-Pro-Gly-Pro)1,6PubChemPubChem compound record: ACTH (4-7), Pro-Gly-Pro-. C37H51N9O10S · MW 813.9 g/mol..
  2. In 110 ischemic-stroke patients followed for 5 months, semax raised plasma BDNF and was associated with better Barthel index outcomes, especially with early rehabilitation2.
  3. A 1997 study added semax to therapy in 30 acute stroke patients and compared them with 80 conventionally treated controls, reporting faster neurological recovery3.
  4. In rats after focal brain ischemia, semax mainly altered immune-response genes, plus 24 vascular genes at 3 hours4.
  5. FDA lists semax among withdrawn compounding nominations and lacks sufficient information to know whether it would cause harm in humans7FDACertain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026..

Written by Residue Editorial Team

Reviewed by Residue Editorial Team · source-by-source check,

First published

Last updated

Registry data · How we grade · Markdown + sources

What is Semax, chemically?

Identifiers retrieved from PubChem.
PubChem CID9811102 “ACTH (4-7), Pro-Gly-Pro-”
FormulaC37H51N9O10S
Molecular weight813.9 g/mol
CAS (as listed)80714-61-0
FDA UNIII5FAL2585H
InChIKeyAFEHBIGDWIGTEH-AQRCPPRCSA-N
Length7 residues
MechanismACTH(4-7) analog; proposed neuroimmune and neurotrophic (BDNF) effects
  • Hydrophobic
  • Basic (+)
  • Acidic (−)
  • Gly / Pro / Cys
Figure 1. Residue sequence of Semax (7 positions) as recorded in PubChem CID 9811102 — H-Met-Glu-His-Phe-Pro-Gly-Pro-OH.

What is semax?

Semax is a synthetic peptide consisting of the ACTH(4-7) fragment and the tripeptide Pro-Gly-Pro (PGP)1. PubChem gives its sequence as Met-Glu-His-Phe-Pro-Gly-Pro (Figure 1)6. Earlier papers describe it as a synthetic derivative of ACTH(4-10)3. It shares its PGP tail with selank.

How is Semax thought to work?

Transcriptome studies in rats with permanent middle-cerebral-artery occlusion found that semax predominantly enhanced expression of immune-system genes — over half of all semax-altered genes — including immunoglobulins and chemokines, and altered 24 vascular-system genes at 3 hours and 12 at 24 hours4. A follow-up study proposed that semax's neuroprotection runs through neuroimmune crosstalk, and found that PGP alone attenuated immune activity1.

What have studies found?

Acute stroke (1997). Thirty patients in the acute period of hemispheric ischemic stroke received semax in combined intensive therapy; 80 patients with comparable strokes received conventional therapy. The authors reported faster regression of general cerebral and focal, especially motor, deficits, with EEG and evoked-potential monitoring3. The comparison was not described as randomized.

Stroke rehabilitation (2018). In 110 patients followed for five months after ischemic stroke, semax raised plasma BDNF levels that stayed high throughout; semax and high BDNF were associated with faster improvement and better final Barthel index scores, and early rehabilitation strengthened the effect2.

Registration. ClinicalTrials.gov returned no study for semax at our fetch5.

Is Semax FDA-approved?

Table 1. Regulatory status of Semax in the United States — from Drugs@FDA (openFDA) and FDA’s bulk-substance compounding categories, as fetched.
RecordStatusSource
FDA approval No approved application Drugs@FDA returned no application for “Semax”. openFDA
Compounding: nominated, then withdrawn
Semax (heptapeptide)		 Withdrawn nomination FDA still lists its safety concerns:
“Compounded drugs containing semax (heptapeptide) may pose risk for immunogenicity for certain routes of administration due to the potential for aggregation and peptide-related impurities. FDA has no, or limited, safety-related information for proposed routes of administration. Therefore, the agency lacks sufficient information to know whether the drug would cause harm if administered to humans.”		 7

FDA's entry for "Semax (heptapeptide)" notes possible immunogenicity from aggregation and peptide-related impurities, and states FDA has no, or limited, safety-related information for proposed routes, so it lacks sufficient information to know whether the drug would cause harm in humans7.

What is still unknown?

  • Randomized, blinded stroke trials published with full methods in widely indexed journals.
  • Any evidence in healthy people for the cognitive uses it is marketed for.

What effects has Semax shown, by body system?

Each row is graded separately using the Residue evidence scale: a compound can carry an A for one use and a D for another.

Table 2. Research-observed effects of Semax by body system, with the strongest evidence available for each.
SystemWhat was observedGrade
Stroke recoveryImproved functional scores and BDNF levels in Russian clinical studies without large RCTs2,3. C
Brain gene expression (rat)Immune and vascular gene changes after experimental ischemia4,1. D

How much research is there on Semax?

0815 2000: 6 records 2000 2001: 10 records 2002: 5 records 2003: 11 records 2004: 10 records 2005: 8 records 2005 2006: 15 records 2007: 7 records 2008: 8 records 2009: 9 records 2010: 9 records 2010 2011: 5 records 2012: 7 records 2013: 11 records 2014: 7 records 2015: 7 records 2015 2016: 5 records 2017: 9 records 2018: 4 records 2019: 3 records 2020: 7 records 2020 2021: 9 records 2022: 4 records 2023: 3 records 2024: 4 records 2025: 8 records 2025 2026: 8 records (year to date) 2026
Figure 2. PubMed records per publication year matching (semax[tiab]) — 209 in total; peak 15 in 2006. The 2026 bar is year-to-date (hatched). Volume of literature is not evidence of efficacy. Run this query on PubMed.

No studies listing Semax as an intervention were returned by ClinicalTrials.gov at the last fetch.

Figure 3. 0 studies on ClinicalTrials.gov match the registry search semax. Multi-phase studies are counted at their highest phase.

Compare and continue

Questions readers ask

Is semax FDA-approved?

No. FDA lists 'Semax (heptapeptide)' among withdrawn compounding nominations and says it lacks sufficient information to know whether it would cause harm in humans7.

What is semax used for in research?

Mostly ischemic stroke. Russian clinical studies report faster recovery of neurological function3 and higher BDNF with better Barthel scores2.

Is semax nootropic?

It is often marketed that way, but in the records we fetched, human studies are in stroke patients; we found no controlled trial of cognitive enhancement in healthy people8.

How does semax work?

In rats with brain ischemia, it predominantly changed expression of immune-response genes and affected vascular genes, suggesting a neuroimmune mechanism4,1.

References

Every source below was retrieved from its official API or page and cached on the data-edition date. Numbers match the margin notes.

  1. 1 PubMed Medvedeva EV, Dmitrieva VG, Limborska SA, et al. Semax, an analog of ACTH((4-7)), regulates expression of immune response genes during ischemic brain injury in rats. Mol Genet Genomics 2017. PMID 28255762; doi:10.1007/s00438-017-1297-1.
  2. 2 PubMed Gusev EI, Martynov MY, Kostenko EV, et al. [The efficacy of semax in the tretament of patients at different stages of ischemic stroke]. Zh Nevrol Psikhiatr Im S S Korsakova 2018. PMID 29798983; doi:10.17116/jnevro20181183261-68.
  3. 3 PubMed Gusev EI, Skvortsova VI, Miasoedov NF, et al. [Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]. Zh Nevrol Psikhiatr Im S S Korsakova 1997. PMID 11517472.
  4. 4 PubMed Medvedeva EV, Dmitrieva VG, Povarova OV, et al. The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. BMC Genomics 2014. PMID 24661604; doi:10.1186/1471-2164-15-228.
  5. 5 ClinicalTrials.gov ClinicalTrials.gov registry search: semax. 0 registered studies at fetch.
  6. 6 PubChem PubChem compound record: ACTH (4-7), Pro-Gly-Pro-. C37H51N9O10S · MW 813.9 g/mol.
  7. 7 FDA Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026.
  8. 8 PubMed PubMed search: (semax[tiab]). 209 records at fetch. PMID semax.