# Semax - Canonical: https://residue.info/c/semax/ - Also called: ACTH(4-7)Pro-Gly-Pro, Met-Glu-His-Phe-Pro-Gly-Pro - Evidence grade: C (Limited / early human data). Small clinical studies in stroke published in Russian journals, without large randomized controlled trials; mechanism work is in rats. - Status: Not FDA-approved · FDA compounding nomination withdrawn - PubChem CID: 9811102 - Updated: 2026-10-19 · Reviewed by: Residue Editorial Team Semax is a synthetic heptapeptide made of the ACTH(4-7) fragment plus the tripeptide Pro-Gly-Pro [1]. Russian clinical studies in ischemic stroke report faster functional recovery and higher BDNF levels with semax added to treatment [2][3]; rat studies link it to immune and vascular gene expression after brain ischemia [4]. It is not FDA-approved, and ClinicalTrials.gov lists no registered study [5]. ## Key findings - Semax consists of ACTH(4-7) linked to Pro-Gly-Pro (sequence Met-Glu-His-Phe-Pro-Gly-Pro) [1][6]. (anchor: https://residue.info/c/semax/#kf-pmid-28255762) - In 110 ischemic-stroke patients followed for 5 months, semax raised plasma BDNF and was associated with better Barthel index outcomes, especially with early rehabilitation [2]. (anchor: https://residue.info/c/semax/#kf-pmid-29798983) - A 1997 study added semax to therapy in 30 acute stroke patients and compared them with 80 conventionally treated controls, reporting faster neurological recovery [3]. (anchor: https://residue.info/c/semax/#kf-pmid-11517472) - In rats after focal brain ischemia, semax mainly altered immune-response genes, plus 24 vascular genes at 3 hours [4]. (anchor: https://residue.info/c/semax/#kf-pmid-24661604) - FDA lists semax among withdrawn compounding nominations and lacks sufficient information to know whether it would cause harm in humans [7]. (anchor: https://residue.info/c/semax/#kf-fda-cat2) ## Effects by system - Stroke recovery (grade C): Improved functional scores and BDNF levels in Russian clinical studies without large RCTs [2][3]. (anchor: https://residue.info/c/semax/#effect-stroke-recovery) - Brain gene expression (rat) (grade D): Immune and vascular gene changes after experimental ischemia [4][1]. (anchor: https://residue.info/c/semax/#effect-brain-gene-expression-rat) ## 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 hours [4]. A follow-up study proposed that semax's neuroprotection runs through neuroimmune crosstalk, and found that PGP alone attenuated immune activity [1]. ## 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 monitoring [3]. 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 effect [2]. **Registration.** ClinicalTrials.gov returned no study for semax at our fetch [5]. 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 humans [7]. ## 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. ## Frequently asked questions **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 humans [7]. **What is semax used for in research?** Mostly ischemic stroke. Russian clinical studies report faster recovery of neurological function [3] and higher BDNF with better Barthel scores [2]. **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 people [8]. **How does semax work?** In rats with brain ischemia, it predominantly changed expression of immune-response genes and affected vascular genes, suggesting a neuroimmune mechanism [4][1]. ## Sources [1] Semax, 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. https://pubmed.ncbi.nlm.nih.gov/28255762/ [2] [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. https://pubmed.ncbi.nlm.nih.gov/29798983/ [3] [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. https://pubmed.ncbi.nlm.nih.gov/11517472/ [4] The 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. https://pubmed.ncbi.nlm.nih.gov/24661604/ [5] ClinicalTrials.gov registry search: semax. 0 registered studies at fetch. https://clinicaltrials.gov/search?intr=semax [6] PubChem compound record: ACTH (4-7), Pro-Gly-Pro-. C37H51N9O10S · MW 813.9 g/mol. https://pubchem.ncbi.nlm.nih.gov/compound/9811102 [7] Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks [8] PubMed search: (semax[tiab]). 209 records at fetch. https://pubmed.ncbi.nlm.nih.gov/?term=(semax%5Btiab%5D) --- From Residue. Research and education only; not medical advice. Quote with attribution and a link to the canonical page.