# Cortagen — Research Peptide Profile

> Cortagen (Ala-Glu-Asp-Pro) is a Khavinson tetrapeptide modeled on brain cortex extract. Rat nerve regeneration and ischemia data, chromatin findings, safety status.

Source: https://peptpedia.org/peptide/cortagen | Published: 2026-09-18 | Last updated: 2026-09-18

Cortagen is a Khavinson-class tetrapeptide (Ala-Glu-Asp-Pro) designed as a minimal synthetic analog of the bovine brain cortex extract Cortexin. Rat studies report faster sciatic nerve regeneration and protection in chronic cerebral ischemia, and ex vivo work describes chromatin decondensation in lymphocytes from elderly donors. No human trial or pharmacokinetic study has been published.

## Overview

Cortagen (Ala-Glu-Asp-Pro) is a synthetic tetrapeptide obtained by directed chemical synthesis based on the amino acid composition of Cortexin, a polypeptide preparation from bovine brain cortex, and belongs to the Khavinson family of short peptide bioregulators. Its best-documented finding is acceleration of peripheral nerve repair: in rats with transected sciatic nerve, 10 mcg/kg intramuscularly for 10 days increased regenerating fiber growth rate by 27% and conduction velocity by 40%. A rat chronic cerebral ischemia study reported faster behavioral recovery and restrained lipid peroxidation in brain tissue, antioxidant experiments ran it alongside the pineal tetrapeptide [Epithalon](/peptide/epithalon) with comparable free-radical effects, and microarray analysis in mice found 234 cardiac transcripts with altered expression after five days of dosing. Cytogenetic studies describe decondensation of age-condensed chromatin in lymphocytes from donors aged 75 to 88. All evidence originates from the St. Petersburg and Tbilisi bioregulation research network; no independent replication and no human clinical trial have been published.

## Molecular Profile

- **Category:** bioregulators
- **Molecular formula:** C17H26N4O9
- **Molecular weight:** 430.4 g/mol
- **CAS number:** 335591-03-2
- **Amino acid sequence:** Ala-Glu-Asp-Pro
- **Also known as:** AEDP, Ala-Glu-Asp-Pro, H-Ala-Glu-Asp-Pro-OH
- **Half-life:** Not established; no pharmacokinetic study published
- **Solubility:** Water-soluble short polar peptide; no formal solubility study published
- **Storage:** Store lyophilized at -20°C.

## Mechanism of Action

No receptor-level target has been identified for Cortagen. The proposing laboratory's framework holds that short peptides penetrate cells, reach the nucleus, and interact directly with DNA, nucleosomes, and promoter regions, modulating gene expression in a tissue-biased pattern; fluorescence-labeled peptides of this class have been observed entering the cytoplasm, nucleus, and nucleolus of living cells. The microarray observation of broad transcriptional change after five days of dosing is cited by the group as supporting evidence. Separately, Cortagen showed antioxidant behavior in rats, reducing lipid peroxidation products and oxidative modification of proteins in serum and cerebral cortex. None of these mechanistic claims has structural-biology confirmation or independent laboratory replication.

## Key Research Findings

- Cortagen is a defined tetrapeptide (Ala-Glu-Asp-Pro) created by directed synthesis from the amino acid composition of Cortexin, replacing an inconsistently characterized bovine brain extract with a single molecule.
- In rats with transected sciatic nerve, 10 mcg/kg intramuscular Cortagen for 10 days increased regenerating fiber growth rate by 27% and conduction velocity by 40%, the primary dose-response finding in its literature.
- Five days of Cortagen dosing in mice altered expression of 234 cardiac transcripts on microarray, cited by the originating group as evidence that short peptides act through broad gene-expression modulation.
- All Cortagen evidence originates from one research network; no independent laboratory replication, human trial, or pharmacokinetic study has been published.

## Cortagen Pharmacokinetics: No Published Data in Any Species

No formal pharmacokinetic study, meaning no measured half-life, bioavailability, distribution, or clearance value, has been published for Cortagen in any species. As an unmodified linear tetrapeptide of L-amino acids it is expected to degrade rapidly in plasma, yet the originating laboratory's framework holds that brief exposure can trigger durable gene-expression effects.

### What the Literature Actually Contains

- The only published dosing regimen is 10 mcg/kg intramuscularly once daily for 10 days in rats after sciatic nerve transection; plasma concentrations were never measured (PMID 11276314).
- A microarray study dosed mice for five consecutive days and detected altered expression of 234 cardiac transcripts, implying systemic exposure from peripheral injection, again without concentration measurements (PMID 15159690).
- Any half-life figure circulating for Cortagen in secondary sources is an extrapolation from tetrapeptide-class behavior, not a measured value.

### The Transient-Trigger Hypothesis and Its Limits

- The Khavinson group's systematic review proposes that short peptides penetrate cells, reach the nucleus, and modulate gene expression through direct DNA and nucleosome interaction, so biological effects could outlast plasma presence (PMID 34834147).
- Consistent with cell penetration being plausible for this class, fluorescence-labeled short Khavinson peptides were observed entering the cytoplasm, nucleus, and nucleolus of HeLa cells (PMID 22117547).
- This hypothesis has never been tested with formal pharmacokinetic-pharmacodynamic modeling for Cortagen, and dosing schedules extrapolated to humans have no experimental basis.

## Safety & Tolerability

Cortagen has no published human safety data of any kind: no clinical trial, no pharmacokinetic study, and no structured adverse-event reporting in the animal work. Rat studies at 10 mcg/kg reported functional benefits without described toxicity, but absence of reported harm in small preclinical studies is not evidence of safety. It is an unapproved research compound.

**Human data status:** No human clinical trials have been published. Human-related data are limited to ex vivo experiments on lymphocytes from elderly donors; the introduction of one 2004 paper from the developing laboratory references therapeutic use in human posttraumatic nerve recovery, but no peer-reviewed clinical study documenting that use is available.

**Regulatory status:** Not approved for human use by the FDA, EMA, or any other major regulatory agency; no verified pharmaceutical registration. Sold as a research compound.

- In the rat sciatic nerve study, Cortagen at 10 mcg/kg intramuscularly for 10 days improved regeneration endpoints; the report contains no structured adverse-event assessment, so tolerability cannot be inferred beyond the absence of noted toxicity. (evidence tier: animal; [PMID 11276314](https://pubmed.ncbi.nlm.nih.gov/11276314/))
- In a rat chronic cerebral ischemia model, Cortagen and Cortexin accelerated behavioral recovery and limited lipid peroxidation in brain tissue without reported toxicity, but the study reported no formal safety endpoints. (evidence tier: animal; [PMID 21476278](https://pubmed.ncbi.nlm.nih.gov/21476278/))
- Human-cell data are ex vivo chromatin studies in lymphocytes from donors aged 75 to 88; these measure cytogenetic endpoints, not safety or tolerability. (evidence tier: in-vitro; [PMID 15085253](https://pubmed.ncbi.nlm.nih.gov/15085253/))
- The proposing group's framework holds that short peptides modulate gene expression through direct DNA and chromatin interaction; the long-term consequences of deliberately altering chromatin state, including any influence on tumor-suppression mechanisms, have never been studied for Cortagen. (evidence tier: theoretical; [PMID 34834147](https://pubmed.ncbi.nlm.nih.gov/34834147/))

## Dosing Information (Research Context)

The only published experimental regimen is 10 mcg/kg intramuscularly once daily for 10 days in rats following sciatic nerve transection. No human dosing protocol exists, no pharmacokinetic study has been published in any species, and dosing schedules circulating in community sources have no peer-reviewed basis.

| Route | Dose | Frequency | Notes |
| --- | --- | --- | --- |
| Intramuscular (rat) | 10 mcg/kg | Daily × 10 days | Only published regimen, from the sciatic nerve transection study; no human dosing established |

## Researched Effects

- **Peripheral Nerve Regeneration** (evidence: preliminary): The defining Cortagen experiment is a rat sciatic nerve transection study in which intramuscular injection at 10 mcg/kg daily for 10 days increased the growth rate of regenerating nerve fibers by 27% and conduction velocity by 40% relative to untreated controls. This remains the only published dose-response finding for the peptide and the basis of research interest in peripheral nerve repair. The work was performed at the Pavlov Institute of Physiology together with the St. Petersburg Institute of Bioregulation and Gerontology and has not been independently replicated. No human nerve-repair trial has been published, although the introduction of a later microarray paper from the same network references therapeutic use after peripheral nerve injury without a citable clinical study.
- **Cerebral Ischemia Protection** (evidence: preliminary): In a rat chronic cerebral ischemia model, Cortagen and its parent extract Cortexin both accelerated recovery of disturbed individual behavior and prevented excessive activation of lipid peroxidation and the decline of antioxidant activity in brain tissue, in animals with both high and low resistance to hypoxia. The authors proposed both agents as correctors of functional and metabolic brain disorders in chronic ischemia. These findings place Cortagen in the neuroprotection research space occupied by its parent preparation, which carries its own clinical literature in Russia, but the synthetic tetrapeptide itself has no published human cerebrovascular study and no independent confirmation of the animal finding.
- **Antioxidant and Free-Radical Modulation** (evidence: preliminary): Injections of Cortagen to rats decreased the content of lipid peroxidation products and reduced oxidative modification of proteins in serum and cerebral cortex, paralleled by suppression of antioxidant enzyme activity, a pattern the author interpreted as reduced oxidative pressure rather than compensatory enzyme upregulation. Epithalon produced a similar profile in the same experiments. This finding is consistent with the ischemia study's observation of restrained lipid peroxidation and represents the compound's principal biochemical characterization outside cytogenetic work. The experiment did not include dose-ranging, so the potency and duration of the antioxidant effect are uncharacterized.
- **Chromatin Decondensation in Aged Cells** (evidence: preliminary): Ex vivo exposure of lymphocytes from donors aged 75 to 88 years to Cortagen produced decondensation of densely packed chromatin fibrils, activation of ribosomal genes, and release of genes repressed by age-related euchromatin condensation, effects the Khavinson and Lezhava groups call deheterochromatinization. A 2023 follow-up from the Tbilisi State University group reported the same direction of effect nearly two decades later, using differential scanning calorimetry and cytogenetic markers. These findings underpin the epigenetic bioregulator hypothesis for Cortagen, but they measure structural chromatin change in cells removed from donors, not functional or clinical outcomes in living organisms.
- **Broad Transcriptional Modulation** (evidence: preliminary): A microarray experiment in female CBA mice found that five consecutive days of Cortagen dosing altered the expression of 234 cardiac transcripts, about 1.5% of the 15,247 transcripts analyzed, corresponding to 110 known genes across multiple functional categories. The study was designed to map molecular targets of the peptide outside its nominal target tissue and is cited by its authors as evidence that short peptides produce systemic gene-expression effects. No follow-up validation with orthogonal methods, dose-response mapping, or protein-level confirmation is indexed in PubMed, and the functional significance of the observed transcriptional changes remains unknown.

## Research Applications

- Neuroscience Research
- Nerve Regeneration
- Gerontology
- Epigenetics Research

## Key Studies

### Effect of tetrapeptide cortagen on regeneration of sciatic nerve

Turchaninova LN, Kolosova LI, Malinin VV, et al. — *Bulletin of Experimental Biology and Medicine* (2000) — [PMID 11276314](https://pubmed.ncbi.nlm.nih.gov/11276314/)

This study is the primary experimental finding in the Cortagen literature and the source of the only published dosing regimen. Following transection and suturing of the sciatic nerve in rats, intramuscular injection of Cortagen at 10 mcg/kg daily for 10 days increased the growth rate of regenerating nerve fibers by 27% and conduction velocity by 40% compared with untreated controls. The work was conducted at the Pavlov Institute of Physiology with the Institute of Bioregulation and Gerontology in St. Petersburg. The report contains no structured adverse-event assessment, and no follow-up dose-ranging or replication study is indexed in PubMed.

### Cortexin and cortagen as correcting agents in functional and metabolic disorders in the brain in chronic ischemia

Zarubina IV, Shabanov PD — *Eksperimental'naia i Klinicheskaia Farmakologiia* (2011) — [PMID 21476278](https://pubmed.ncbi.nlm.nih.gov/21476278/)

This rat study compared the bovine cortex polypeptide drug Cortexin with its synthetic minimal analog Cortagen in a chronic cerebral ischemia model. Both agents accelerated recovery of disturbed individual behavior in ischemic rats regardless of whether the animals were high or low resistant to hypoxia, and both prevented excessive activation of lipid peroxidation and the associated decrease of antioxidant activity in brain tissues. The authors proposed that Cortexin and Cortagen could increase the efficacy of neuroprotective therapy in chronic brain ischemia. The study did not report formal safety endpoints and has not been independently replicated.

### Effects of bioactive tetrapeptides on free-radical processes

Kozina LS — *Bulletin of Experimental Biology and Medicine* (2007) — [PMID 18239817](https://pubmed.ncbi.nlm.nih.gov/18239817/) | [doi:10.1007/s10517-007-0230-8](https://doi.org/10.1007/s10517-007-0230-8)

This experiment administered Epithalon and Cortagen to rats and measured free-radical process markers in serum and cerebral cortex. Both tetrapeptides decreased the content of lipid peroxidation products and reduced oxidative modification of proteins, and this was paralleled by suppression of antioxidant enzyme activity, a combination the author interpreted as a lower oxidative burden requiring less compensatory enzyme defense rather than as direct enzyme inhibition. The study provides the principal biochemical antioxidant characterization of Cortagen, though without dose-ranging or time-course detail in the English abstract.

### Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarray

Anisimov SV, Khavinson VKh, Anisimov VN — *Neuro Endocrinology Letters* (2004) — [PMID 15159690](https://pubmed.ncbi.nlm.nih.gov/15159690/)

This study documents both the origin and the systemic transcriptional reach of Cortagen. The authors state the tetrapeptide was obtained by directed synthesis based on amino acid analysis of the natural brain cortex preparation Cortexin, and they profiled 15,247 transcripts in the hearts of female CBA mice after five consecutive days of Cortagen injections. Comparative microarray analysis identified 234 clones (1.53% of those analyzed) with significantly altered expression, matching 110 known genes across various functional categories. The paper's introduction also references therapeutic effects in human posttraumatic peripheral nerve recovery, though no corresponding peer-reviewed clinical study is indexed. The work is cited as evidence that a short peptide can produce broad gene-expression changes in a tissue distant from its nominal target.

### Effects of short peptides on lymphocyte chromatin in senile subjects

Khavinson VKh, Lezhava TA, Malinin VV — *Bulletin of Experimental Biology and Medicine* (2004) — [PMID 15085253](https://pubmed.ncbi.nlm.nih.gov/15085253/) | [doi:10.1023/b:bebm.0000024393.40560.05](https://doi.org/10.1023/b:bebm.0000024393.40560.05)

This cytogenetic study exposed leukocytes from donors aged 75 to 88 years to five synthetic short peptides (Vilon, Epithalon, Livagen, Prostamax, and Cortagen) and measured chromatin endpoints. All five peptides induced activation of ribosomal genes, decondensation of densely packed chromatin fibrils, and release of genes repressed through age-specific condensation of euchromatic regions. Epithalon, Livagen, and Prostamax additionally decondensed pericentromeric structural heterochromatin of chromosome 1, with Epithalon and Livagen also affecting chromosome 9. The study is a core piece of evidence for the shared chromatin-level mechanism proposed across the Khavinson peptide family, while measuring structural endpoints rather than functional outcomes.

### Epigenetic modification under the influence of peptide bioregulators on the old chromatin

Lezhava T, Jokhadze T, Monaselidze J, et al. — *Georgian Medical News* (2023) — [PMID 37042594](https://pubmed.ncbi.nlm.nih.gov/37042594/)

Nearly two decades after the original chromatin studies, the Tbilisi State University group re-examined the effect of peptide bioregulators (Epitalon, Livagen, Cortagen, and Vilon) on condensed chromatin in lymphocyte cultures from donors aged 75 to 88 years, using differential scanning calorimetry, nucleolar organizer activity, pericentromeric heterochromatin polymorphism, and sister chromatid exchange as readouts. The authors report that aging is accompanied by progressive heterochromatinization of chromosomes, and that the peptide bioregulators induced decondensation of total heterochromatin. The paper restates the group's framework in which age-related chromatin condensation deactivates previously functioning genes, and positions short peptides as epigenetic modifiers of that process.

## Frequently Asked Questions

### What is Cortagen?

Cortagen is a synthetic tetrapeptide with the sequence Ala-Glu-Asp-Pro (AEDP). It was created by directed chemical synthesis based on the amino acid composition of Cortexin, a natural polypeptide preparation from bovine brain cortex, and belongs to the Khavinson class of short peptide bioregulators. It is studied as a research compound in peripheral nerve regeneration, cerebral ischemia, and chromatin biology. It is not approved for human use in any country.

### What did the Cortagen sciatic nerve study find?

The primary Cortagen experiment (PMID: 11276314) transected and sutured the sciatic nerve in rats, then administered 10 mcg/kg intramuscularly once daily for 10 days. Regenerating nerve fiber growth rate increased by 27% and conduction velocity by 40% versus untreated controls. This is the only published dose-response finding for Cortagen and the origin of the 10 mcg/kg figure that circulates in research communities. No equivalent human study exists.

### How is Cortagen different from Cortexin?

Cortexin is a mixture of polypeptides extracted from bovine brain cortex and carries its own clinical literature in Russia. Cortagen is a single defined molecule (Ala-Glu-Asp-Pro) synthesized to reproduce elements of the extract's activity. A 2011 rat study compared them directly in chronic cerebral ischemia and found that both accelerated behavioral recovery and limited lipid peroxidation in brain tissue (PMID: 21476278), but comparable efficacy in humans has never been tested.

### Has Cortagen been studied in humans?

No peer-reviewed human clinical trial of Cortagen has been published. The introduction of a 2004 microarray paper from the developing laboratory states that Cortagen showed a therapeutic effect in human posttraumatic peripheral nerve recovery, but no citable clinical study is indexed in PubMed (PMID: 15159690). Human-related evidence is limited to ex vivo experiments on lymphocytes from elderly donors, where Cortagen altered chromatin structure (PMID: 15085253).

### Is Cortagen safe?

Safety is unestablished. There is no toxicology study, no structured adverse-event reporting in the animal work, no pharmacokinetic study, and no human trial. Rat studies at 10 mcg/kg reported functional benefits without described toxicity, but small preclinical studies without safety endpoints cannot demonstrate safety. Cortagen is an unapproved research compound.

## Related Peptides

- [Epithalon](https://peptpedia.org/peptide/epithalon)
- [Cerebrolysin](https://peptpedia.org/peptide/cerebrolysin)
- [Pinealon](https://peptpedia.org/peptide/pinealon)
- [Cardiogen](https://peptpedia.org/peptide/cardiogen)

---

This content is for educational and research purposes only. It is not medical advice, and the compounds covered are research chemicals not approved for human use unless explicitly stated otherwise.

Cite this page: Peptpedia — Research Peptide Encyclopedia, https://peptpedia.org