4AA Preclinical
Cardiogen
Synthetic cardiac tetrapeptide (Ala-Glu-Asp-Arg) from the Khavinson school that stimulates cardiomyocyte proliferation, suppresses p53-mediated apoptosis, and modulates fibrosis in animal and in-vitro heart-tissue models.
In Plain English:
Cardiogen is a four-amino-acid chain — alanine, glutamic acid, aspartic acid, and arginine — synthesised by directed analysis of the cardiac muscle proteome at the St. Petersburg Institute of Bioregulation and Gerontology. In organotypic tissue-culture experiments using rat heart from both young (3-month) and old (24-month) animals, cardiogen outperformed all 20 individual amino acids in stimulating myocardial cell proliferation, and immunohistochemistry showed it concurrently reduced p53 expression — the chief apoptosis trigger in stressed cardiomyocytes. A second animal study found dose-dependent inhibition of M-1 sarcoma growth in aged rats via haemorrhagic necrosis and tumour-cell apoptosis, suggesting tissue-selective rather than blanket anti-apoptotic activity. A 2022 Khavinson-group review names AEDR as a peptide candidate for regulating the senescence-associated secretory phenotype (SASP) in cardiovascular cells and inflammaging. No human clinical trial has been published. All evidence is preclinical, generated exclusively in Russian-affiliated laboratories, and should be treated as hypothesis-generating only.
Research Maturity
Preclinical (~5–8 peer-reviewed papers (2009–2022), all single-lab Russian; no human trials or independent replication+ Studies)
Focus
Cardiovascular Health
Cell Protection
Origin
Identified and synthesised by Vladimir Kh. Khavinson and colleagues at the St. Petersburg Institute of Bioregulation and Gerontology, Russia, as part of the 'cytogen' directed-synthesis programme. The programme isolated the minimal bioactive amino-acid sequence from organ-specific polypeptide extracts (the parent extract is Cardialen, from cardiac muscle). AEDR was selected because compositional analysis of heart-muscle peptides revealed enrichment of Ala, Glu, Asp, and Arg at regulatory gene promoter sites. A Russian Federation patent on the compound (Patent RF № 2255756, filed by Khavinson VKh et al.) covers its use as a myocardial-function-restoring peptide compound. Introduced commercially as Cardiogen® (TD Peptid Bio / St. Petersburg Institute capsule form, 60 × 0.275 g capsules, ~€69 per pack) and as a lyophilised research powder by Western peptide vendors from approximately 2018 onward.
Mechanism
Penetrates cell nuclei and binds specific DNA sequence motifs in the promoter regions of cardiac-expressed genes — consistent with Khavinson-group chromatin interaction studies showing preferential binding to GC-rich promoter regions and N-terminal motifs of histone proteins H1, H2B, H3, and H4 (PMID 34834147 contextualises the class mechanism). In cardiac tissue this is proposed to increase transcriptional availability of genes governing cardiomyocyte differentiation, contractile protein synthesis, and mitochondrial bioenergetics. Experimentally confirmed effects include: (1) stimulation of cardiomyocyte proliferation in organotypic culture from both young and aged rats at 10⁻¹² M (picomolar) concentrations — an effect not reproducible by any single amino acid in isolation (PMID 20210190); (2) downregulation of p53 protein expression by immunohistochemistry, interpreted as inhibition of the intrinsic apoptosis pathway (PMID 20210190); (3) upregulation of cytoskeletal proteins — actin, vimentin, tubulin — reported up to 5-fold in treated cells; (4) upregulation of nuclear matrix proteins lamin A/C up to 2.5-fold; (5) modulation of collagen and elastin synthesis in cardiac fibroblasts, shifting them toward a less fibrotic phenotype; (6) normalisation of CXCL12, WEDC1, and ghrelin signalling factor expression in aging human prostate fibroblasts treated alongside two cognate peptides (PMID 20586252), indicating broader fibroblast-regulatory activity; (7) a 2022 Khavinson review explicitly lists AEDR among peptides with potential to regulate SASP markers including IL-6, TGF-β1, NF-κB, and p53 in cardiovascular cells (PMID 36611900). In tumour tissue the mechanism inverts: cardiogen increases apoptosis in M-1 sarcoma cells and drives haemorrhagic necrosis through the tumour vascular network rather than direct cytostatic action (PMID 20396706).
Outcome
Cardiomyocyte proliferation rate in organotypic tissue culture from young and old rats (PMID 20210190, in vitro, picomolar concentration); p53 protein expression in myocardial tissue — decreased, indicating apoptosis inhibition (PMID 20210190); cytoskeletal protein levels (actin, vimentin, tubulin) — up to 5-fold increase in treated cells (various Khavinson-affiliated reports); lamin A/C nuclear matrix protein — up to 2.5-fold increase; cardiac-injury mortality — reported 3-fold reduction vs control in an experimentally induced myocardial injury rodent model (Atlas of Science summary, primary citation not independently verified); M-1 sarcoma tumour volume — dose-dependent inhibition in aged rats via apoptosis and haemorrhagic necrosis (PMID 20396706); CXCL12/WEDC1/ghrelin expression in aging prostate fibroblast cultures — normalised toward youthful levels (PMID 20586252); SASP biomarker regulation in cardiovascular senescent cells — identified as regulatory target (PMID 36611900).
