# Cardiogen — Research Peptide Profile

> Cardiogen (Ala-Glu-Asp-Arg) is a Khavinson tetrapeptide bioregulator for cardiac tissue. All evidence is preclinical - see the p53, proliferation & tumor data.

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

Cardiogen (Ala-Glu-Asp-Arg) is a Khavinson tetrapeptide assigned to cardiac tissue. Published evidence is entirely preclinical: it stimulated proliferation in myocardial explants from young and old rats, lowered p53 expression, and slowed M-1 sarcoma growth in rodents. No human studies of any kind exist.

## Overview

Cardiogen is a synthetic tetrapeptide (Ala-Glu-Asp-Arg) developed within the Khavinson bioregulator program and assigned, under the program's tissue-specificity hypothesis, to cardiac tissue. It was characterized in organotypic culture work at the St. Petersburg Institute of Bioregulation and Gerontology, the group that also developed [Epithalon](/peptide/epithalon), where it stimulated growth of myocardial explants from both young and old rats at concentrations as low as 0.05 ng/ml and 10^-12 M, and reduced expression of the pro-apoptotic protein p53. A separate line of work reported dose-dependent inhibition of M-1 sarcoma growth in aged rats, apparently through effects on the tumor vascular network rather than direct cytotoxicity. Reviews from the same research lineage place the AEDR tetrapeptide among peptides proposed to regulate senescence-associated secretory phenotype signaling and inflammaging in cardiovascular cells. All published evidence is preclinical; no human studies have been published, and injectable dosing protocols circulating in research communities have no documented basis in the literature.

## Molecular Profile

- **Category:** bioregulators
- **Molecular formula:** C18H31N7O9
- **Molecular weight:** 489.5 g/mol
- **Amino acid sequence:** Ala-Glu-Asp-Arg
- **Also known as:** AEDR, Ala-Glu-Asp-Arg, AEDR tetrapeptide
- **Half-life:** Not established; no published pharmacokinetic data in any species
- **Solubility:** Soluble in water (formal solubility characterization not published)
- **Storage:** Store lyophilized at -20°C.

## Mechanism of Action

Cardiogen is proposed to act through the short-peptide epigenetic mechanism common to the Khavinson bioregulator class: cellular uptake followed by interaction with DNA or chromatin-associated proteins and modulation of gene expression. Molecular docking identified AEDR as one of the most efficient computed ligands of the LAT1 and LAT2 amino acid transporters and the PEPT1 peptide transporter, a proposed uptake route for ultrashort peptides. In myocardial explants, cardiogen lowered p53 protein expression, interpreted as suppression of apoptosis in cardiac tissue, and stimulated proliferation in tissue from young and old animals alike. In the M-1 sarcoma model it produced the opposite effect in malignant tissue, increasing tumor-cell apoptosis and hemorrhagic necrosis, with morphological evidence pointing to the tumor vascular network as the site of action. This context-dependent behavior, anti-apoptotic in normal myocardium but pro-apoptotic in tumor tissue, is the defining and still mechanistically unexplained feature of its pharmacology.

## Key Research Findings

- Cardiogen (Ala-Glu-Asp-Arg) stimulated proliferation in myocardial tissue cultures from both young and old rats at 10^-12 M, while only 2 of 20 individual amino acids showed any activity in aged tissue.
- The same organotypic culture work found cardiogen reduced p53 protein expression, interpreted as suppression of apoptosis in cardiac tissue.
- In senescent rats with transplanted M-1 sarcoma, cardiogen produced dose-dependent tumor growth inhibition via hemorrhagic necrosis and stimulated tumor-cell apoptosis, acting through the tumor vascular network rather than direct cytotoxicity.
- Molecular docking identified AEDR among the most efficient computed peptide ligands of the LAT1, LAT2, and PEPT1 transporters, a proposed cellular uptake route for ultrashort bioregulator peptides.

## Safety & Tolerability

Cardiogen has never been studied in humans, and no formal safety, pharmacokinetic, or toxicology data exist in any species. Rodent and cell-culture studies report biological activity without describing harm at the doses used, but its reported suppression of p53, a central tumor-suppressor protein, in normal cardiac tissue is a theoretical long-term concern that has never been investigated.

**Human data status:** No human data of any kind: no clinical trials, no observational human studies, and no published case reports exist. All evidence is from rat studies and cell or organotypic cultures.

**Regulatory status:** Not approved for human use by any regulatory agency; a preclinical research compound.

- In organotypic myocardial cultures from young and old rats, cardiogen at 10^-12 M stimulated proliferation and reduced p53 protein expression, interpreted as apoptosis inhibition; because p53 is a central tumor suppressor, chronic suppression in healthy tissue is a recognized theoretical oncologic concern that has not been studied. (evidence tier: animal; [PMID 20210190](https://pubmed.ncbi.nlm.nih.gov/20210190/))
- In senescent rats with transplanted M-1 sarcoma, cardiogen injections produced dose-dependent tumor growth inhibition through hemorrhagic necrosis and increased tumor-cell apoptosis without a direct cytostatic effect; systemic safety parameters were not the focus of the report. (evidence tier: animal; [PMID 20396706](https://pubmed.ncbi.nlm.nih.gov/20396706/))
- Reviews from the developing research group propose the AEDR tetrapeptide as a regulator of senescence-associated inflammatory signaling in cardiovascular cells; this mechanistic rationale has not been tested in controlled human studies, and no human exposure data exist. (evidence tier: theoretical; [PMID 36611900](https://pubmed.ncbi.nlm.nih.gov/36611900/))

## Dosing Information (Research Context)

No human dosing has been established. Published preclinical work used organotypic tissue cultures with cardiogen at 0.05 ng/ml or 10^-12 M, and injections in tumor-bearing rats in the M-1 sarcoma experiments. There are no published pharmacokinetic data in any species, and community-derived subcutaneous protocols using milligram doses every few days have no basis in the peer-reviewed literature.

## Researched Effects

- **Cardiac Cell Proliferation** (evidence: preliminary): Organotypic culture research demonstrates Cardiogen's capacity to stimulate cell proliferation in myocardial tissue across the lifespan. In explants from 3-month and 24-month old rats, the tetrapeptide at a concentration of 10^-12 M produced a strong stimulating effect on proliferation in tissue from both age groups, while only 2 of 20 individual amino acids tested showed any activity in old tissue. Earlier work from the same program found cardiogen effective at 0.05 ng/ml in heart explant cultures from young and aged rats, a tissue-selective pattern shared with the other panel peptides in their corresponding organs. These findings have implications for research into age-related loss of cardiac regenerative capacity and the design of tissue-specific peptide interventions.
- **Apoptosis Modulation via p53** (evidence: preliminary): Immunohistochemical analysis in the myocardial explant studies showed that Cardiogen decreased p53 protein expression, which the authors interpret as inhibition of apoptosis in cardiac tissue. Because p53 drives programmed cell death in damaged and senescent cells, its suppression is proposed as a mechanism for preserving cardiomyocyte populations in aging myocardium. The same p53 pathway is a central tumor-suppressor mechanism, however, so chronic suppression in healthy tissue carries a recognized theoretical concern that has never been experimentally addressed for this peptide. These apoptosis-modulation findings are relevant to cardiac aging research, ischemia-reperfusion models, and the broader study of how ultrashort peptides influence cell-death signaling.
- **Tumor-Modifying Effects in Rodents** (evidence: preliminary): A dedicated oncology experiment found that Cardiogen injections produced dose-dependent inhibition of M-1 sarcoma growth in senescent rats, with tumor-cell apoptosis levels higher in all treated groups than in controls. Morphological analysis showed the inhibition was caused by hemorrhagic necrosis developing in the tumor and by stimulated apoptosis, while proliferative parameters indicated no direct cytostatic effect of the peptide on tumor cells. The authors concluded the effect is realized through the tumor vascular network, an indirect anti-tumor mechanism distinct from cytotoxic chemotherapy. These tumor-modifying findings are preliminary, come from a single transplanted-tumor model, and have implications for research into peptide effects on tumor angiogenesis and vascular stability.
- **Tissue-Specific Reparative Signaling** (evidence: preliminary): Cardiogen was one of four synthetic bioregulator peptides, alongside bronchogen, prostamax, and pancragen, shown to stimulate organotypic cultures specifically of their corresponding target organs, heart, lung, prostate, and pancreas respectively, from young and aged rats at an effective concentration of 0.05 ng/ml. This tissue-specificity pattern is the experimental foundation of the Khavinson school claim that ultrashort peptides carry organ-selective regulatory information. The authors proposed such peptides as candidates for stimulating reparative processes in the corresponding tissues during aging. Independent laboratories have not replicated the tissue-specificity phenomenon, and it remains a signature but unverified claim of the developing research lineage.
- **Cellular Uptake Through Peptide Transporters** (evidence: preliminary): Computational work addressed how ultrashort peptides like Cardiogen could enter cells to exert their proposed intracellular effects. Molecular modeling and docking of 26 biologically active ultrashort peptides against the ligand-binding sites of the LAT1 and LAT2 amino acid transporters and the PEPT1 peptide transporter found that AEDR, alongside EDR, KEDP, and related peptides with charged N-terminal and neutral or positive C-terminal residues, ranks among the most efficient computed ligands, in several cases scoring higher than the transporters' known substrates. While docking results require experimental confirmation, they provide the first plausible uptake route explaining how a hydrophilic tetrapeptide could reach intracellular targets and interact with genomic machinery.

## Research Applications

- Cardiovascular Research
- Aging Research
- Cell Culture Models
- Oncology Research

## Key Studies

### The Effect of the Amino Acids and Cardiogen on the Development of Myocard Tissue Culture from Young and Old Rats

Chalisova NI, Lesniak VV, Balykina NA, et al. — *Advances in Gerontology* (2009) — [PMID 20210190](https://pubmed.ncbi.nlm.nih.gov/20210190/)

This Russian-language organotypic culture study compared all 20 proteinogenic amino acids against the synthetic tetrapeptide cardiogen at 10^-12 M in myocardial explants from 3-month and 24-month old rats. Seven amino acids stimulated cell proliferation in young-rat myocardium, but only two remained active in old-rat tissue, whereas cardiogen demonstrated the strongest stimulating effect on proliferation in tissues from both age groups. Immunohistochemical analysis showed cardiogen decreased p53 protein expression, which the authors interpret as inhibition of apoptosis in myocardial tissue. The study is the primary evidence for cardiogen's assignment to cardiac tissue within the bioregulator program.

### Tumor-Modifying Effect of Cardiogen Peptide on M-1 Sarcoma in Senescent Rats

Levdik NV, Knyazkin IV — *Bulletin of Experimental Biology and Medicine* (2009) — [PMID 20396706](https://pubmed.ncbi.nlm.nih.gov/20396706/) | [doi:10.1007/s10517-010-0730-9](https://doi.org/10.1007/s10517-010-0730-9)

This in vivo study tested cardiogen in senescent rats bearing transplanted M-1 sarcoma. Tumor-cell apoptosis after cardiogen injections was higher in all experimental groups than in controls, and dose-dependent inhibition of tumor growth was driven by the development of hemorrhagic necrosis and stimulation of tumor-cell apoptosis. Proliferative-activity parameters showed the growth inhibition was not caused by a direct cytostatic effect on the tumor, and morphological signs pointed to a specific mechanism realized through the tumor vascular network. The result is notable because it shows the peptide promoting apoptosis in malignant tissue while suppressing it in normal myocardium, a context dependence that remains mechanistically unexplained.

### The Tissue-Specific Effect of Synthetic Peptides-Biologic Regulators in Organotypic Tissues Culture in Young and Old Rats

Zakutskii AN, Chalisova NI, Ryzhak GA, et al. — *Advances in Gerontology* (2006) — [PMID 17152728](https://pubmed.ncbi.nlm.nih.gov/17152728/)

This Russian-language study tested four synthetic bioregulator peptides, cardiogen, bronchogen, prostamax, and pancragen, in organotypic cultures of heart, lung, prostate, and pancreas explants from young (3-week) and aged (18-month) rats. Each peptide at an effective concentration of 0.05 ng/ml showed a stimulating effect in its corresponding target tissue compared with control explants, in both age groups. The authors conclude these bioregulatory peptides are candidates for clinical stimulation of reparative processes in the appropriate tissues during aging. This is the foundational experiment for the tissue-specificity claim that defines the Khavinson bioregulator class.

### Senescence-Associated Secretory Phenotype of Cardiovascular System Cells and Inflammaging: Perspectives of Peptide Regulation

Khavinson V, Linkova N, Dyatlova A, et al. — *Cells* (2022) — [PMID 36611900](https://pubmed.ncbi.nlm.nih.gov/36611900/) | [doi:10.3390/cells12010106](https://doi.org/10.3390/cells12010106)

This open-access review analyzes how the senescence-associated secretory phenotype (SASP) and low-grade inflammation of aging contribute to atherosclerosis, coronary heart disease, and myocardial infarction, cataloging the signaling molecules involved: anti-proliferative proteins p16, p19, p21, p38, and p53, inflammatory cytokines IL-1, IL-6, IL-8, IL-18, TNF-α, and TGF-β1, matrix metalloproteinases, adhesion molecules, and sirtuins. It identifies the AEDR tetrapeptide (cardiogen), the KED tripeptide, and several vasoprotective polypeptides as regulators of SASP and inflammaging molecule synthesis in cardiovascular cells, and argues for peptide-based drug development against age-associated cardiovascular pathology. As a review from the developing group, it frames rather than tests the cardiogen evidence.

### Feasibility of Transport of 26 Biologically Active Ultrashort Peptides via LAT and PEPT Family Transporters

Khavinson VK, Linkova NS, Rudskoy AI, Petukhov MG — *Biomolecules* (2023) — [PMID 36979488](https://pubmed.ncbi.nlm.nih.gov/36979488/) | [doi:10.3390/biom13030552](https://doi.org/10.3390/biom13030552)

This molecular-modeling study docked 26 biologically active ultrashort peptides, plus all 8,400 possible di- and tri-peptides as a comparator set, into the ligand-binding sites of the LAT1 and LAT2 amino acid transporters and the PEPT1 peptide transporter. The 26 bioactive peptides, including the AEDR tetrapeptide (cardiogen) and EDR tripeptide (pinealon), systematically outscored peptides with no established biological activity, and AEDR was among the most effective computed ligands, in several cases scoring above known transporter substrates and inhibitors. The work proposes LAT and PEPT family transporters as the cellular uptake route that could deliver ultrashort peptides to the intracellular and nuclear targets implied by their observed bioactivity.

## Frequently Asked Questions

### Has Cardiogen been studied in humans?

No. As of 2026 there are no human studies of cardiogen of any kind: no clinical trials, no observational human data, and no published case reports. All published evidence is preclinical, consisting of organotypic tissue-culture experiments and rodent studies from the St. Petersburg research lineage. Human pharmacokinetics, effective exposure, and safety are entirely uncharacterized, and community-derived injection protocols have no documented basis in the peer-reviewed literature.

### How does Cardiogen affect p53 and apoptosis?

In myocardial explants from young and old rats, cardiogen at 10^-12 M reduced p53 protein expression, interpreted as suppression of apoptosis in cardiac tissue (PMID: 20210190). In contrast, in rats with transplanted M-1 sarcoma it increased tumor-cell apoptosis and produced hemorrhagic tumor necrosis through effects on the tumor vascular network (PMID: 20396706). This context-dependent pattern, anti-apoptotic in normal myocardium but pro-apoptotic in tumor tissue, is unexplained. It also cuts both ways for safety: chronic p53 suppression in healthy tissue would be a theoretical oncologic concern, and that question has never been studied.

### What is the evidence for Cardiogen's tissue specificity?

The tissue-specificity claim rests on a 2006 organotypic culture study (PMID: 17152728) in which cardiogen, bronchogen, prostamax, and pancragen each stimulated growth only in explants of their corresponding organs (heart, lung, prostate, pancreas) from both young and aged rats, at 0.05 ng/ml. This experiment is the foundation of the Khavinson school claim that ultrashort peptides carry organ-selective regulatory information. The phenomenon has not been replicated by independent laboratories, so it should be regarded as a signature claim of the developing group rather than an established fact.

### Is there a published Cardiogen dosing protocol?

No. Published studies used cardiogen at 0.05 ng/ml and 10^-12 M in organotypic tissue cultures, and by injection in tumor-bearing rats without a translational dosing framework. No pharmacokinetic study exists in any species, so there is no basis for converting cell-culture concentrations into whole-organism doses. Subcutaneous milligram-dose protocols circulating in research communities are community-derived and have no support in the published literature.

### How does Cardiogen relate to other Khavinson bioregulators?

Cardiogen (Ala-Glu-Asp-Arg) belongs to the ultrashort-peptide panel developed at the St. Petersburg Institute of Bioregulation and Gerontology, the same program behind Epithalon, pinealon, and cartalax. Within the program's framework, each short peptide is assigned to a target tissue: cardiogen to heart, bronchogen to lung, pancragen to pancreas, prostamax to prostate. A 2023 molecular-docking study (PMID: 36979488) found that cardiogen and several class members are efficient computed ligands of the LAT1, LAT2, and PEPT1 transporters, a proposed shared cellular uptake route for the class.

## Related Peptides

- [Epithalon](https://peptpedia.org/peptide/epithalon)
- [Vesugen](https://peptpedia.org/peptide/vesugen)
- [SS-31](https://peptpedia.org/peptide/ss-31)
- [Cartalax](https://peptpedia.org/peptide/cartalax)

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