Epitalon (Epithalon, AEDG) vs FOXO4-DRI

Epitalon (Epithalon, AEDG)

Epitalon, also spelled epithalon, is the synthetic tetrapeptide Ala-Glu-Asp-Gly, modelled on epithalamin, a peptide extract of bovine pineal gland. It came out of a Russian research programme on short regulatory peptides, and nearly all of the published work comes from that programme and its collaborators. The studies include cultured human cells, rodents and fruit flies, together with some human studies reported mostly in Russian-language journals. The topics are ageing biology, telomere maintenance and pineal function. Independent replication outside that group is limited, and the human data are sparse and come almost entirely from the same source.

FOXO4-DRI

FOXO4-DRI is a 46-residue D-retro-inverso peptide designed to interfere with the interaction between the FOXO4 protein and p53. It was reported in 2017 by Baar and colleagues, who took part of the FOXO4 p53-interaction domain, joined it to a cell-penetrating sequence and built the whole peptide from D-amino acids. All published work is preclinical: cultured human cells, mouse models of ageing and of lung fibrosis, and one rodent study in which clearing senescent cells made pulmonary haemodynamics worse. No human study was identified.

How Epitalon (Epithalon, AEDG) acts

No receptor for Epitalon has been identified, and most mechanistic proposals come from the same research school. Cell-culture studies from that group have reported induction of telomerase activity and telomere elongation in human somatic cells, which normally express little telomerase. Other papers propose that short peptides of this kind enter the nucleus and bind DNA or histones, altering the expression of particular genes; this idea has not been widely tested elsewhere. Animal studies have examined melatonin secretion by the pineal gland and circadian markers. The overall picture rests on a narrow base of laboratories.

How FOXO4-DRI acts

Baar and colleagues reported in 2017 that FOXO4 holds p53 in the nucleus of senescent cells, and that a peptide competing for that interaction causes p53 to leave the nucleus, followed by apoptosis in senescent cells selectively. Solution NMR work published in 2025 placed the binding site on the disordered transactivation domain of p53 and found that both the FOXO4-derived region and the cationic carrier sequence contribute. Selectivity for senescent cells is reported by several groups, in cell and rodent models only.

The records side by side

• Type: Epitalon (Epithalon, AEDG), Tetrapeptide; FOXO4-DRI, D-retro-inverso peptide
• Length: Epitalon (Epithalon, AEDG), 4 amino acids; FOXO4-DRI, 46 amino acids
• Molecular weight: Epitalon (Epithalon, AEDG), 390.35 g/mol; FOXO4-DRI, 5358 g/mol
• Molecular formula: Epitalon (Epithalon, AEDG), C14H22N4O9; FOXO4-DRI, C228H388N86O64

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.