Cortagen and peptide bioregulators — what do studies say?

Four amino acids whose order was arrived at not in a structural laboratory but from the amino acid composition of an extract of calf cerebral cortex. That is how Cortagen came about, and with it the whole family of “peptide bioregulators”: Epitalon for the pineal gland, Cardiogen for the heart, Bronchogen for the bronchi, Livagen for the liver. One institute, one author on most of the publications and one hypothesis, according to which short peptides enter the cell nucleus and bind to DNA.

This article explains what the concept is and where it came from, what has been written about Cortagen in experimental work, how Cardiogen and Bronchogen differ from it and, most importantly, how to judge the quality of this evidence: how much independent replication there is and how much self-citation. It ends with the regulatory and anti-doping status of the whole group. We write nothing about methods of use or the quantities in protocols; the FAQ section explains why.

In our catalogue, the compounds discussed in this article are chemical reagents intended solely for laboratory research (Research Use Only). They are not medicinal products, dietary supplements or foods, and they are not intended for use in humans or animals. What this status means is explained in our material on the legal status of research reagents.

What peptide bioregulators are

The concept comes from St Petersburg, from the institute of bioregulation and gerontology led by Vladimir Khavinson. Its first stage was the 1970s and 1980s: complex peptide preparations called cytomedins were obtained from animal tissues, among them Epithalamin from the pineal gland, Thymalin from the thymus and Cortexin from the cerebral cortex. The second stage was synthesis: on the basis of the amino acid analysis of those extracts, short peptides of two to four amino acids were designed to reproduce the action of the parent preparation. Khavinson described this path in a 2002 monograph, from extraction technology to “novel principles of the design of biologically active short peptides possessing tissue-specific activity” (Khavinson, 2002, PMID 12374906).

Hence the names. Cortagen (Ala-Glu-Asp-Pro, AEDP) corresponds to Cortexin, Epitalon (AEDG) to Epithalamin, Cardiogen (AEDR) to a heart extract, Bronchogen (AEDL) to a bronchial extract. The authors based the principle of “tissue specificity” on organotypic cultures: each peptide stimulated the growth of explants from the tissue whose preparation had been used to design it (Khavinson, 2001, PMID 11713572). The mechanism the school proposes is bold: the peptides are said to cross the cell and nuclear membranes, bind to DNA and histones and regulate gene expression; the team’s own systematic review from 2021 summarises this view (Khavinson et al., 2021, PMID 34834147). The evidence for DNA binding comes from computer docking, which for 19 peptides pointed to short sequences, for instance “agat” for KE and EDP (Khavinson et al., 2016, PMID 27909961), and from fluorescence measurements of labelled peptides in HeLa cells (Fedoreyeva et al., 2011, PMID 22117547).

Cortagen: what has been described

Chemically it is the tetrapeptide Ala-Glu-Asp-Pro, C₁₇H₂₆N₄O₉, mass 430.4 g/mol (PubChem CID 18439621). A PubMed query for Cortagen and its sequence returns 20 records (7 November 2026), some of which concern a different compound with the same abbreviation, the AEDP reagent used in nanoparticle chemistry. The genuine papers on the peptide number a dozen or so, almost all involving the St Petersburg institute or its collaborators.

The most cited thread is nerve regeneration. In rats whose sciatic nerve had been cut and sutured, ten days of treatment with the peptide increased the growth rate of fibres by 27% and conduction velocity by 40% (Turchaninova et al., 2000, PMID 11276314); a delayed effect was also described (Kolosova et al., 2002, PMID 12134478). A 2004 paper states that “in humans, Cortagen demonstrated a pronounced therapeutic effect” on post-traumatic recovery of peripheral nerves, but does not cite the study from which the sentence comes; its actual subject was the mouse heart transcriptome, in which treatment with the peptide changed the expression of 234 clones corresponding to 110 known genes (Anisimov et al., 2004, PMID 15159690).

In the brain of rats with chronic ischaemia, Cortagen and Cortexin accelerated behavioural recovery and curbed lipid peroxidation (Zarubina and Shabanov, 2011, PMID 21476278); a fall in peroxidation products and oxidative protein modification was also described in rat serum and cerebral cortex (Kozina, 2007, PMID 18239817). In the immune system the results are weaker than for its relatives: in mouse splenocytes Cortagen stimulated interleukin-2 mRNA synthesis less than Vilon and Epitalon (Kazakova et al., 2002, PMID 12447482), it had no effect at all on thymocytes (Khavinson et al., 2002, PMID 12420072), and in chickens after removal of the pituitary, in which Epitalon corrected the immune and clotting disturbances, Cortagen changed none of the parameters studied (Kuznik et al., 2008, PMID 19432169). That last paper is instructive: two peptides differing by a single amino acid gave starkly different results, which undermines any simple interchangeability of “bioregulators”.

The only data with human material are cultures of lymphocytes from people aged 75 to 88. All the peptides tested, Cortagen among them, activated ribosomal genes in these cells and loosened condensed chromatin (Khavinson et al., 2004, PMID 15085253); a Georgian team collaborating with the institute repeated these observations with cytogenetic methods (Lezhava et al., 2020, PMID 33526740). These are studies of cells in glassware, not studies in people.

Cardiogen and Bronchogen in brief

Cardiogen (Ala-Glu-Asp-Arg) has the thinnest literature. In organotypic culture of heart muscle from young and old rats it stimulated proliferation and lowered expression of the p53 protein (Chalisova et al., 2009, PMID 20210190), and in old rats with transplanted M-1 sarcoma it inhibited tumour growth through haemorrhagic necrosis and apoptosis, which the authors linked to an action on the tumour’s vessels (Levdik and Knyazkin, 2009, PMID 20396706). A 2022 review lists AEDR among peptides that regulate molecules of the secretory phenotype of senescent cells in the cardiovascular system (Khavinson et al., 2022, PMID 36611900).

Bronchogen (Ala-Glu-Asp-Leu; written Ala-Asp-Glu-Leu in one paper) has the most interesting set of data, because it reaches beyond animal tissue. In a rat model of chronic obstructive pulmonary disease induced by nitrogen dioxide, a month of treatment reversed the remodelling of the bronchial epithelium and neutrophilic inflammation (Kuzubova et al., 2015, PMID 26468022). In ageing cultures of human bronchial epithelial cells it stimulated differentiation factors (Khavinson et al., 2012, PMID 22808515), it raised the melting temperature of calf DNA by 3.1 °C (Monaselidze et al., 2011, PMID 21240358), and in tobacco cultures, together with Epitalon, it stimulated callus and leaf growth and altered the expression of plant developmental genes (Fedoreyeva et al., 2017, PMID 28371610). The same peptide therefore acts on rat bronchi, human cells and tobacco tissue. For the authors this is proof of a universal epigenetic mechanism. For the reader it is a signal that the “tissue specificity” in the preparation’s name does not describe what the data show.

Quality of the evidence: where the studies come from and how much replication there is

The whole family shares the structure of literature that we described in the case of Epitalon: most papers come from a single centre, a large proportion appeared in Russian gerontology journals, and the reviews summarising the body of work are written by the same authors or their students. A 2026 review in Current Aging Science summarising “many years of research” on bioregulators was produced at the same institute (Arutjunyan et al., 2026, PMID 42839866). The independent groups that appear in the bibliography are collaborators from Tbilisi and Moscow publishing together with Khavinson. We found no replication by a centre unconnected with the concept’s originators.

The second feature is the absence of clinical trials in the accessible registries. ClinicalTrials.gov holds no study of Cortagen, Cardiogen or Bronchogen, nor of the term “peptide bioregulator” (queried on 7 November 2026). Claims of effects in humans, such as the sentence on nerve recovery in the 2004 paper, have no counterpart in PubMed in the form of a published controlled study. The third feature is the language: the reviews speak of “geroprotection” and of raising the “physiological resource” by 20 to 42% (Khavinson, 2014, PMID 25306656), without stating how that quantity was measured. How to read such promises across the whole category of compounds studied in connection with ageing is explained in our longevity guide; our pillar on nootropic substances places short nootropic peptides, Cortagen among them, against racetams and cholinergic compounds.

A fair summary, then: Cortagen is a tetrapeptide with documented activity in several animal and cell models, with results that depend on the experimental system, originate from a single scientific school and have not been independently confirmed. That is less than the descriptions of a “brain peptide” promise, and as much as the data say.

Regulatory status

European Union. The EU medicines data that EMA publishes under Article 57 (data as of 9 October 2026) contain neither Cortagen, Cardiogen nor Bronchogen; the only “Cardiogen” hit in the EMA data is Cardiogen-82, a rubidium generator for diagnostic imaging that has nothing to do with the peptide. Nor do the peptides have authorisation as food or food supplement ingredients in the EU.

United States. The Drugs@FDA database lists no product containing Cortagen, Cardiogen or Bronchogen (checked 7 November 2026).

Other countries. Cortexin, the parent preparation, is a different matter. In the Russian register of medicines Cortexin® appears as a prescription medicine of the company Geropharm, composed of “polypeptides of bovine cerebral cortex”, as a lyophilisate, with marketing authorisations from March 2022 (GRLS, as of 23 October 2026). That is a medicine made of the mixture of peptides in the extract, not the four-amino-acid Cortagen; the names sound alike, but they are two different regulatory entities. No approval of Cortagen itself as a medicine is known to us in any country. The reagent in our catalogue is material for laboratory research. The identity of a batch, meaning that its sequence matches, is confirmed by an analytical document; how to read it is explained in our article on the certificate of analysis.

Anti-doping note

The WADA 2026 Prohibited List does not name Cortagen, Cardiogen or Bronchogen. Class S0 decides: any pharmacological substance with no approval by any governmental regulatory health authority for human therapeutic use is prohibited at all times. None of the three peptides holds such approval, so all fall under S0. The 2027 List, in force from 1 January 2027, keeps that criterion and adds the word “peptides” explicitly to the description of class S0; WADA’s explanatory note states that many peptides not approved for human use meet the List’s criteria and belong to S0 or to other classes even when not named (2027 List and Summary of Major Modifications). Cortexin’s registration in Russia concerns a different product and does not change Cortagen’s status. Athletes tested in the United States fall under the same List, because USADA is a signatory to the World Anti-Doping Code. The classification rules are set out in our guide to the WADA Prohibited List; the decision rests with WADA and the national agencies.

Frequently asked questions

What is Cortagen?
A synthetic tetrapeptide, Ala-Glu-Asp-Pro, designed in St Petersburg from the amino acid composition of a cerebral cortex extract, Cortexin. It belongs to the family of “peptide bioregulators” together with Epitalon, Cardiogen and Bronchogen.

Is Cortagen the same thing as Cortexin?
No. Cortexin is a prescription medicine registered in Russia, made of a mixture of polypeptides from bovine cerebral cortex extract. Cortagen is a single four-amino-acid peptide with no approval as a medicine in any country known to us.

Have peptide bioregulators been studied in humans?
The ClinicalTrials.gov registry holds no study of Cortagen, Cardiogen or Bronchogen. The data with human material are cell cultures, and the sentences about clinical effects in the reviews do not point to published controlled studies.

How do Cardiogen and Bronchogen differ from Cortagen?
By one amino acid at the end of the chain: Pro in Cortagen, Arg in Cardiogen, Leu in Bronchogen. According to the bioregulation school this difference determines tissue specificity, yet Bronchogen also acted on plant cells, which is hard to square with simple specificity.

Why do we not describe how and in what quantities these peptides were used?
Because all the data come from protocols in animals and cultures, and the reagents in our catalogue are laboratory material that is not administered to humans or animals outside a study. None of these peptides has gone through the procedure in which such values are established for a person.

Is Cortagen prohibited in sport?
Yes. As a substance without approval for human use it falls under class S0 of the Prohibited List, in the 2026 and 2027 editions, at all times. The same applies to Cardiogen and Bronchogen.

Summary

Peptide bioregulators are the concept of a single institute: short peptides designed from the composition of tissue extracts which, according to their authors, regulate gene expression by binding to DNA. Cortagen, designed on the basis of Cortexin, has a dozen or so experimental papers, from nerve regeneration in rats to the mouse heart transcriptome, with weaker results than Epitalon in the immune system and no effect in chickens after pituitary removal. Cardiogen has the poorest literature, Bronchogen the most varied, including action on plants. Common to the family are the absence of independent replication, the absence of clinical trials in the registries and the absence of approval as a medicine; only Cortexin, a different product, is registered. In sport all three peptides fall under class S0 in both editions of the List.

Product documentation

Reagent pages with batch documentation: Cortagen 20 mg, Cortagen spray, Cardiogen and Bronchogen. Compounds of this family appear in the categories reagents in the context of immunity, area: brain, area: heart and area: lungs. The identity and purity of each batch are confirmed by a certificate of analysis.

Bibliography

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15. Lezhava T, Jokhadze T, Monaselidze J, et al. Epigenetic modification under the influence of peptide bioregulators on “aged” heterochromatin. Georgian Med News. 2020;(309):120-124. PMID: 33526740
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