Semax (Met-Glu-His-Phe-Pro-Gly-Pro): what it is, where it comes from, and what the published studies measured

What Semax is: sequence and molecular weight#

Semax is a synthetic peptide of seven amino acids: methionine, glutamic acid, histidine, phenylalanine, proline, glycine and proline, written Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP). The first four residues, Met-Glu-His-Phe, are a fragment of adrenocorticotropic hormone (ACTH) spanning positions 4 to 7. The last three, Pro-Gly-Pro (often shortened to PGP), were added by its designers to make the peptide more resistant to breakdown by peptidases.^[1][2] That is why the literature uses two names for the same molecule: some papers call it ACTH(4-7)PGP, and others, including its developers' earlier titles, describe it as an analogue of ACTH(4-10).^[2][3]

In chemical databases the free peptide has the molecular formula C37H51N9O10S and a monoisotopic mass of 813.348 Da.^[1] Its average molecular weight is 813.9 g/mol, its CAS registry number is 80714-61-0 and its PubChem compound identifier is 9811102; these are the values listed on the Semax product page, with the free peptide as the basis. Research suppliers usually provide Semax as a lyophilized powder, often as a salt such as the acetate, and the salt form changes the mass of material per milligram of peptide. The lot's Certificate of Analysis is where the form should be stated.

Where Semax comes from#

Semax is a product of Russian peptide research, and its literature is closely tied to one institution. The papers summarized on this page, and a 2018 review of Semax research from 1980 to 2016, all include authors from the Institute of Molecular Genetics of the Russian Academy of Sciences in Moscow, among them N. F. Myasoedov, who appears on each of them.^[2][3][4][5] Most of that work was published in Russian journals or in English by the same groups.

Those authors describe Semax as a drug already in clinical use in Russia. The 2020 transcriptome paper states that it "has been used in neurological practice for many years", and a 2009 paper from the same institute states that it had been used clinically for stroke, brain hypoxia and brain trauma.^[2][4] These are statements by the developing groups. FDA's 2026 briefing document on Semax separately states that it is a registered drug in Russia.^[6]

Semax and the FDA#

Semax is not an FDA-approved drug. It appears on the FDA's page of bulk drug substances that may present significant safety risks in pharmacy compounding, in the table of substances that were previously in category 2 and whose nominations were later withdrawn by the nominators. The FDA's entry says that compounded drugs containing Semax may pose a risk of immunogenicity for certain routes because of the potential for aggregation and peptide-related impurities, that the agency has no or limited safety information for the proposed routes, and that it therefore lacks sufficient information to know whether the substance would cause harm if administered to humans.^[7]

Semax was later evaluated for FDA's 503A bulk drug substances list, the list of substances that pharmacies may use in compounding. FDA's briefing document for the July 2026 meeting of its Pharmacy Compounding Advisory Committee concluded that the evaluation criteria weigh against placing either Semax (free base) or Semax acetate on the list, and noted that neither is a component of an FDA-approved drug.^[6] At the meeting on July 24, 2026, the committee voted 8 to 5 to recommend adding Semax. Committee votes are nonbinding recommendations, and formal rulemaking is required before any substance is added to the list.^[8] As of this writing, the FDA safety-risk page cited above still shows Semax in the withdrawn-nominations table.^[7]

Semax BDNF research in rats#

The most cited strand of Semax research concerns brain-derived neurotrophic factor (BDNF), a protein involved in the survival and growth of nerve cells, and TrkB, the receptor BDNF binds. Two 2006 papers from the Institute of Molecular Genetics and collaborators set out the main findings. Both are rat studies; no people were involved.

Dolotov et al., Journal of Neurochemistry, 2006#

This study asked two questions. First, does Semax bind to brain tissue in a specific way? Using radiolabeled peptide and membranes prepared from rat basal forebrain, the authors reported binding that was time-dependent, specific and reversible, and that depended on calcium. Second, does Semax change BDNF levels in that brain region? Rats given the peptide showed higher BDNF protein in the basal forebrain three hours later, but not in the cerebellum, which the authors used as a comparison region. The authors suggested that the BDNF change could account for part of the behavioral activity reported for Semax in rodents, which is their reading of their own data, not a tested conclusion.^[3]

Dolotov et al., Brain Research, 2006#

The companion paper moved to the rat hippocampus. It measured BDNF protein, activation (phosphorylation) of the TrkB receptor, and messenger RNA for BDNF and TrkB, including the BDNF transcript that begins at exon III, one of several alternative starting points for the BDNF gene. The reported changes were increases in BDNF protein, TrkB phosphorylation and exon III BDNF and TrkB mRNA after a single administration.^[9]

Semax in rat models of experimental stroke#

The second strand uses rat models of cerebral ischemia, in which blood flow to part of the brain is cut off by blocking the middle cerebral artery. These are standard laboratory models of stroke. The question in these papers is not whether Semax does anything for a person; it is which genes in the damaged rat brain change their activity when the peptide is present.

Dmitrieva et al., Cellular and Molecular Neurobiology, 2009#

Adult male Wistar rats underwent permanent occlusion of the middle cerebral artery and received Semax, the PGP tripeptide on its own, or saline. Sham-operated and non-operated rats served as further controls. At 3, 24 and 72 hours the authors measured messenger RNA for three neurotrophins (BDNF, NT-3 and NGF) and their receptors (TrkA, TrkB and TrkC) in the frontoparietal cortex by reverse-transcription and real-time PCR. Both Semax and PGP changed the transcription of these genes after ischemia, with partly overlapping patterns; the effects of Semax were more confined to the ischemic cortex, and those of PGP less specific.^[4] Including PGP alone is a useful design choice, because it tests how much of the activity belongs to the stabilizing tail rather than the ACTH fragment.

Filippenkov et al., Genes, 2020#

This study used a transient model: the middle cerebral artery of male Wistar rats was blocked for 90 minutes and then reopened, so that the brain experienced both ischemia and reperfusion. The authors used RNA sequencing (RNA-Seq) to measure gene expression across the whole transcriptome of subcortical tissue, checked ten genes by real-time PCR, and confirmed lesions by histology and MRI. They reported no significant differences at 4.5 hours, and 394 differentially expressed genes (191 up, 203 down, above a 1.5-fold change) at 24 hours in Semax-treated animals. Genes linked to inflammation tended to be lower and genes linked to neurotransmission higher, roughly the reverse of the pattern caused by ischemia-reperfusion alone. Each RNA-Seq comparison group contained three animals.^[2]

What human data exists for Semax#

There are clinical reports, and they come almost entirely from Russian neurology. The most recent one we could open is a 2018 paper by Gusev and colleagues in the Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, published in Russian with an English abstract.^[10] It followed 110 patients after ischemic stroke, divided into an early-rehabilitation group (about three months after the stroke) and a late-rehabilitation group (about seven months after), each split into subgroups that did or did not receive Semax. The study measured plasma BDNF, muscle strength on the British Medical Research Council scale and the Barthel index, a standard score of independence in daily activities. The authors reported higher plasma BDNF in the Semax subgroups and an association between BDNF levels and recovery scores.

That is a description of what the trial studied, not evidence of an effect in people. The abstract we read does not describe randomization or blinding, and it does not say whether the subgroups that did not receive Semax were given a placebo. The 2020 transcriptome paper also cites an earlier 1997 clinical and electrophysiological study by the same research group in acute stroke; we did not open that paper and do not describe it here.^[2]

What has not been studied#

The shape of the evidence matters as much as the findings. Almost all of the published Semax work comes from a small set of Russian institutes, with the Institute of Molecular Genetics at its centre, and the papers summarized here share authors. Independent replication by unconnected groups outside Russia is thin. Mechanistic statements about BDNF, TrkB and gene expression rest on rat brain tissue, and the authors' own papers frame them as proposed explanations.

• No FDA approval; FDA states it lacks sufficient information to know whether Semax would cause harm in humans, and its 2026 briefing concluded the criteria weigh against listing it for compounding.^[7][6]
• No large, randomized, placebo-controlled trials published in international journals among the sources we reviewed.
• The rat findings use specific injury models and short timepoints (hours to days); long-term behavior of the molecule in any species is not described in these studies.
• The clinical literature is mainly in Russian, which limits outside scrutiny of methods and data.

Semax vs Selank#

Semax is often searched alongside Selank, another Russian-developed seven-residue peptide that ends in the same Pro-Gly-Pro tail but starts from a different parent molecule. Our Selank vs Semax comparison sets the two side by side on structure, origin and the state of the evidence.

Reading a Semax listing and its COA#

A listing that describes Semax with words borrowed from the rat literature, or from Russian clinical practice, is presenting research findings as if they were settled. A listing that states the sequence, the form (free peptide or salt), the amount per vial, the lot number and where the lot's analytical report can be read is describing a reagent. For Semax, a Certificate of Analysis should show an HPLC purity figure and a mass-spectrometry result consistent with about 813.9 g/mol for the free peptide, along with the issuing laboratory and date. Our guides to reading a Certificate of Analysis and to HPLC and mass spectrometry explain each item, and the COA library lists every Renuvia lot and its current testing status.