Cardiogen (AEDR) – Research Compound Profile

Cardiogen (AEDR) – Research Compound Profile

Category: Cardiovascular Research | Molecular Type: Synthetic Tetrapeptide Bioregulator (H-Ala-Glu-Asp-Arg-OH) | Research Status: Preclinical & In Vitro

This page compiles published research data for qualified researchers. Cardiogen (AEDR) is sold exclusively as a research compound and is not approved for human use.

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Molecular Overview

Cardiogen (H-Ala-Glu-Asp-Arg-OH, also designated AEDR) is a synthetic tetrapeptide bioregulator developed by Prof. Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology. It comprises four naturally occurring amino acids — alanine, glutamic acid, aspartic acid, and arginine — with a molecular weight of approximately 461 Da [15]. The compound was designed as a candidate tissue-selective gene-expression regulator and belongs to the broader family of Khavinson ultrashort peptide bioregulators that have been the subject of over four decades of research [1][2].

As an ultrashort peptide, Cardiogen’s small molecular size (only four amino acid residues) is a defining characteristic of its pharmacological profile. Molecular modeling studies have demonstrated that the AEDR sequence is capable of forming stable complexes with double-stranded DNA, providing a structural basis for its proposed gene-regulatory activity [10][11]. The compound’s PubChem identifier is CID 11583989 [15].

Structurally, Cardiogen carries two acidic residues (Glu, Asp) and one basic residue (Arg), giving it an amphoteric character with a net charge close to neutral at physiological pH — distinct from the strongly anionic character of the shorter Khavinson tripeptides. It contains no cysteine, methionine, or tryptophan, so oxidative side-chain chemistry is not a relevant degradation pathway; the principal chemical liabilities are amide-bond hydrolysis and, at the aspartate residue, the same succinimide/iso-aspartate rearrangement chemistry documented for other short Asp-containing bioregulator peptides.

Mechanism of Action

Unlike conventional receptor-agonist compounds, Cardiogen has been proposed to operate at the epigenetic level. Published molecular modeling and experimental data indicate that AEDR penetrates cell membranes and enters the nucleus, where it binds directly to histone proteins (H1, H2b, H3, and H4) and interacts with specific DNA sequences in gene promoter regions. This binding is hypothesized to increase the transcriptional availability of genes involved in cardiac tissue maintenance and repair [1][10][11].

At the cellular level, the most thoroughly documented effects of Cardiogen involve cardiomyocyte proliferation and fibroblast regulation. In organotypic tissue culture experiments using cardiac tissue from both young and aged rats, Chalisova et al. (2009) reported that Cardiogen significantly stimulated myocardial cell proliferation — notably even in tissues from old animals, where regenerative capacity is typically diminished [6]. Immunohistochemical analysis in the same study revealed that Cardiogen decreased expression of the p53 tumor suppressor protein in cardiac tissue, suggesting an anti-apoptotic mechanism [6].

In mouse embryonic fibroblast cultures, Khavinson et al. reported that AEDR increased the synthesis of cytoskeletal proteins (actin, tubulin, vimentin) and elevated the nuclear matrix proteins lamin A and lamin C [3][8]. The upregulation of lamin A/C is noteworthy, as these nuclear envelope proteins are critical for maintaining nuclear structural integrity and have been implicated in antiapoptotic cellular pathways.

In a coronary artery ligation model of experimental myocardial infarction in rats, Khavinson et al. (2023) reported that AEDR administration was associated with markedly improved survival relative to untreated controls [3]. The peptide also reduced the size of necrotic zones in cardiac tissue and helped preserve myocardial glycogen stores, indicating preserved cellular energy metabolism under ischemic conditions [3]. Additionally, AEDR has been reported to modulate the senescence-associated secretory phenotype (SASP) in cardiovascular system cells, regulating the synthesis of inflammatory cytokines and matrix metalloproteinases implicated in age-related cardiovascular tissue changes and inflammaging [3].

Khavinson et al. (2021) provided a systematic review of the broader mechanisms by which short peptides regulate gene expression, establishing the theoretical framework within which Cardiogen’s epigenetic activity is understood. The review documented evidence that ultrashort peptides interact with DNA and histone proteins to modulate transcriptional activity in a tissue-specific manner [1].

Interpretive limits: As with other members of the Khavinson ultrashort-peptide class, the proposed direct-DNA-binding mechanism rests principally on molecular modeling and in vitro binding data rather than structural determination inside intact cells [1][10][11]. Nearly all published pharmacology for Cardiogen originates from a single research group, and independent replication outside that group is limited. The organotypic and cell-culture findings are internally consistent, but the causal chain linking AEDR binding to the reported whole-tissue effects has not been independently established.

Published Research Parameters

The following table indexes the study models, durations, and reported observations of selected peer-reviewed publications. This is a bibliographic index only — not a protocol and not a recommendation for any use.

Stability & Storage Characteristics

Published data and standard peptide chemistry principles provide the following stability characteristics for Cardiogen:

• Lyophilized form: Tetrapeptides in lyophilized (freeze-dried) powder form generally demonstrate stability at −20 °C (−4 °F) for extended periods (24+ months) and at 2–8 °C (35.6–46.4 °F) for shorter durations (up to 12 months). Protection from light and moisture is standard for peptide storage [15].
• Solution stability: Once reconstituted in aqueous solution, short peptides are subject to gradual degradation. Refrigerated storage at 2–8 °C (35.6–46.4 °F) is standard practice in research settings to slow hydrolysis and oxidation.
• Freeze-thaw sensitivity: Repeated freeze-thaw cycles can denature peptide structures through ice crystal formation. Aliquoting reconstituted solutions prior to freezing is a common laboratory practice to preserve peptide integrity.
• Molecular characteristics: As a tetrapeptide with a molecular weight of ~461 Da, Cardiogen’s small size is consistent with the reported cellular uptake and nuclear penetration described in molecular modeling studies, where it is proposed to interact with DNA and histones [1][10].
• Principal degradation routes: Amide-bond hydrolysis and aspartate-driven succinimide/iso-aspartate rearrangement are the expected chemical liabilities for this sequence in aqueous solution; buffer pH is accordingly a significant variable for reconstituted-solution stability.
• Visual indicators of degradation: Cloudy, discolored, or particulate-containing solutions may indicate peptide degradation or microbial contamination and are typically discarded in research settings.

Analytical Characterization

Confirming identity and purity for a four-residue peptide of this composition requires a panel suited to small, polar molecules. Reverse-phase HPLC provides the primary purity measure, though ion-pairing reagents are typically needed for adequate retention given the peptide’s mixed acidic/basic character. Electrospray mass spectrometry confirms the intact molecular ion against the expected mass; because the iso-aspartate rearrangement product at the Asp residue is mass-identical to the parent, orthogonal methods (e.g., differential retention on HPLC) are needed to distinguish the two species. Amino-acid analysis after acid hydrolysis confirms the expected 1:1:1:1 residue ratio. Net peptide content, rather than gross vial mass, should be used to establish working concentrations, since counter-ion and residual moisture are a non-trivial fraction of weighed material at this molecular weight.

Key Published Research Findings

• Cardiomyocyte proliferation: In a 2009 Advances in Gerontology study, Chalisova et al. reported that Cardiogen significantly stimulated cardiac tissue proliferation in organotypic culture from both young and aged rats, demonstrating tissue-specific bioregulatory activity even in senescent tissue with typically diminished regenerative capacity [6].

• Anti-apoptotic effects: In the same 2009 study, immunohistochemical analysis revealed that Cardiogen decreased p53 protein expression in myocardial tissue, indicating suppression of programmed cell death in cardiomyocytes [6].

• Post-myocardial infarction survival (rat model): In a 2023 Cells study, Khavinson et al. reported that in a rat coronary artery ligation model, AEDR-treated animals demonstrated markedly improved survival compared to controls, with concurrent reductions in necrotic zone size and preservation of myocardial glycogen stores [3].

• Cytoskeletal and nuclear matrix protein upregulation: Khavinson et al. reported in Bulletin of Experimental Biology and Medicine that AEDR increased synthesis of actin, vimentin, and tubulin, and increased the nuclear matrix proteins lamin A/C, in mouse embryonic fibroblast cultures, consistent with support for cellular structural integrity and proliferative capacity [3][8].

• Anti-fibrotic potential: Data from Chalisova et al. (2009) and the Atlas of Science review (2023) suggest that Cardiogen modulates fibroblast activity, with potential implications for reducing excessive scar formation during cardiac remodeling processes [2][6].

• SASP modulation: In a 2023 Cells review, Khavinson et al. documented that AEDR regulated the synthesis of inflammaging-associated signaling molecules in cardiovascular cells, including pro-inflammatory cytokines and matrix metalloproteinases, of relevance to models of age-related cardiac tissue change [3].

• Anti-tumor observations (animal model): In a 2009 Bulletin of Experimental Biology and Medicine study, Levdik and Knyazkin reported that in senescent rats with transplanted M-1 sarcoma, Cardiogen administration increased tumor cell apoptosis, with tumor growth inhibition mediated through hemorrhagic necrosis [7].

• Epigenetic gene regulation: In a 2021 systematic review in Molecules, Khavinson et al. compiled evidence that ultrashort peptides, including AEDR, interact with histone proteins and DNA promoter regions to modulate tissue-specific gene expression, providing a mechanistic framework for the observed bioregulatory effects [1].

Safety Profile in Published Literature

• Preclinical tolerability: Available preclinical literature reports minimal adverse effects associated with AEDR. As an endogenous-sequence tetrapeptide composed of naturally occurring amino acids, Cardiogen has demonstrated favorable biocompatibility in published cell culture and animal model studies [1][4].
• Toxicology data: No significant toxicity has been documented at the concentration ranges employed in published studies. Anisimov and Khavinson (2010) noted in Biogerontology that the Khavinson bioregulatory peptides as a class have been associated with a favorable safety profile across decades of research [4].
• Clinical observations: Khavinson and colleagues have reported observations involving bioregulatory peptides in Russian research settings, as reviewed in Anisimov and Khavinson (2010) and Khavinson et al. (2023) [4][5]. However, no large-scale, randomized controlled human trials of Cardiogen specifically have been published in the Western peer-reviewed literature as of this writing.
• Limitations of current data: The existing safety profile is based predominantly on in vitro studies, animal models, and limited published observations. No comprehensive drug interaction studies have been published. The absence of Phase I–III clinical trials conducted under international regulatory standards (e.g., FDA, EMA) represents a significant gap in the available safety data.

Regulatory Status

• FDA approval: Cardiogen (AEDR) is not approved by the U.S. Food and Drug Administration (FDA) for any therapeutic indication.
• Clinical trial status: No clinical trials for Cardiogen are currently registered on ClinicalTrials.gov. Published research has been conducted primarily in Russia under the auspices of the St. Petersburg Institute of Bioregulation and Gerontology.
• Research classification: Cardiogen is classified and sold as a research compound intended exclusively for in vitro and preclinical research applications. It is not intended for human consumption, therapeutic use, or self-administration.
• Regulatory context: Researchers working with Cardiogen are responsible for ensuring compliance with all applicable local, national, and institutional regulations governing peptide research.

Research Use Only

All information on this page is provided for informational and citation purposes and summarizes findings from published scientific literature. Cardiogen (AEDR) supplied by IronPeak Peptides LLC is intended for laboratory research purposes only. It is not a drug, food, or cosmetic, is not intended for human or veterinary consumption, and is not intended to diagnose, treat, cure, or prevent any disease. Nothing on this page constitutes medical advice or a recommendation for use in humans. Handling should be performed only by qualified researchers in an appropriate laboratory setting.

References

1. Molecules (2021) — Khavinson VK, Popovich IG, Linkova NS, Mironova ES, Ilina AR. “Peptide Regulation of Gene Expression: A Systematic Review.” Molecules. 26(22):7053. PMID: 34834147. View Source

2. Atlas of Science (2023) — Finn J. “Cardiomyocyte Metabolism Research and Cardiogen Peptide.” Atlas of Science. View Source

3. Cells (2023) — Khavinson V, Linkova N, Dyatlova A, Kantemirova R, Kozlov K. “Senescence-Associated Secretory Phenotype of Cardiovascular System Cells and Inflammaging: Perspectives of Peptide Regulation.” Cells. 12(1):106. PMID: 36611900. View Source

4. Biogerontology (2010) — Anisimov VN, Khavinson VK. “Peptide Bioregulation of Aging: Results and Prospects.” Biogerontology. 11:139–149. PMID: 19830585. View Source

5. Khavinson.info (2023) — Khavinson VK, Linkova NS, Dyatlova AS. “Perspectives of Peptide Regulation.” Review. View Source

6. Advances in Gerontology (2009) — Chalisova NI, Lesniak VV, Balykina NA, et al. “The Effect of the Amino Acids and Cardiogen on the Development of Myocard Tissue Culture from Young and Old Rats.” Adv Gerontol. 22(3):409–413. PMID: 20210190. View Source

7. Bulletin of Experimental Biology and Medicine (2009) — Levdik NV, Knyazkin IV. “Tumor-Modifying Effect of Cardiogen Peptide on M-1 Sarcoma in Senescent Rats.” Bull Exp Biol Med. 148(3):433–436. PMID: 20396706. View Source

8. Bulletin of Experimental Biology and Medicine (2012) — Khavinson VK, et al. “Tetrapeptide H-Ala-Glu-Asp-Arg-OH Stimulates Expression of Cytoskeletal and Nuclear Matrix Proteins.” Bull Exp Biol Med. View Source

9. Bulletin of Experimental Biology and Medicine (2016) — Khavinson VK, et al. “Short Peptides Regulate Gene Expression.” Bull Exp Biol Med. 162(2):288–292. PMID: 27909961. View Source

10. International Journal of Molecular Sciences (2022) — Khavinson VK, et al. “Neuroepigenetic Mechanisms of Action of Ultrashort Peptides in Alzheimer’s Disease.” Int J Mol Sci. 23(8):4259. View Source

11. Molecules (2020) — Khavinson VK, et al. “AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism.” Molecules. 25(3):609. View Source

12. Nature Reviews Cardiology (2019) — Vega RB, Konhilas JP, Kelly DP, Leinwand LA. “Molecular Mechanisms Underlying Cardiac Adaptation to Exercise.” Cell Metab. 25(5):1012–1026. View Source

13. Advances in Gerontology (2010) — Kheifets OV, Polyakova VO, Kvetnoy IM. “Peptidergic Regulation of the Expression of Signal Factors of Fibroblast Differentiation in the Human Prostate Gland in Cell Aging.” Adv Gerontol. 23(1):68–70. PMID: 20586252. View Source

14. Advances in Gerontology (2006) — Chalisova NI, et al. “The Tissue-Specific Effect of Synthetic Peptides—Biologic Regulators in Organotypic Tissues Culture in Young and Old Rats.” Adv Gerontol. 19:80–85. PMID: 17152728. View Source

15. PubChem (2023) — National Center for Biotechnology Information. “PubChem Compound Summary for CID 11583989, H-Ala-Glu-Asp-Arg-OH.” View Source

⚠️ Disclaimer: This page is provided for educational and informational purposes only and does not constitute medical advice, diagnosis, or treatment recommendations. Cardiogen (AEDR) is sold exclusively as a research compound, has not been approved by the FDA for any use, and is not intended for human consumption, self-administration, or any therapeutic application. All information is derived from published peer-reviewed literature. Research must comply with all applicable laws, regulations, and institutional guidelines.

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