Epithalon

Molecular identity

Sequence

Ala-Glu-Asp-Gly

Formula

C14H22N4O9

Molecular weight

390.35 g/mol

CAS

307297-39-8

PubChem CID

219042

What it acts on

• Telomerase and its catalytic subunit — in telomerase-negative human fetal fibroblasts the cited work reports induced expression of the catalytic subunit, appearance of enzymatic activity and telomere elongation, which the authors suggest may be due to reactivation of the telomerase gene in somatic cells.
• Melatonin synthesis in the pineal axis — the 2025 review describes a direct influence on melatonin production, and a second review groups the peptide with compounds said to act on circadian and mitochondrial regulators.
• Interleukin-2 transcription and thymocyte mitogenic activity — the review literature reports altered IL-2 mRNA levels and modulated mitogenic activity of murine thymocytes, the immune arm of the described profile.
• Cholinesterases — AChE and BuChE are listed among the enzymes whose activity the review reports as enhanced, alongside telomerase itself; how a four-residue peptide reaches enzymes this unrelated is not resolved there.
• HER-2/neu expression — in the transgenic mouse study the authors attribute the reduced tumour burden probably to suppression of HER-2/neu expression; this is offered as an interpretation, not as a measured endpoint of that report.

What the studies report

Each item below summarises the paper it is numbered to, written from that paper's own abstract. The badge says how the evidence was produced.

1. 1.
   reviewJ Am Acad Orthop Surg Glob Res Rev (2026)

   A 2026 narrative review of therapeutic peptides in orthopaedics. It reports no new data on this compound: it places Epithalon alongside delta sleep-inducing peptide and pinealon as agents said to target circadian and mitochondrial regulators, within a broader map of PI3K/Akt, mTOR, MAPK, TGF-β and AMPK signalling. The review's own conclusion is the relevant part — preclinical studies look promising, but clinical trials are currently lacking.

2. 2.
   reviewInt J Mol Sci (2025)

   The most comprehensive source in this set: a 2025 review in Int J Mol Sci covering 25 years of in vitro, in vivo and in silico work. It records the peptide's derivation from Epithalamin and the reported effects on melatonin synthesis, IL-2 mRNA levels, murine thymocyte mitogenic activity and the activity of AChE, BuChE and telomerase, framed as a geroprotective and neuroendocrine profile arising from both specific and non-specific mechanisms. The authors state directly that it remains uncertain whether these are the sole mechanisms of action, and that physico-chemical and structural investigation of the peptide is quite limited next to the pharmacodynamic literature.

3. 3.
   animal modelBull Exp Biol Med (2002)

   A lifespan study in female FVB/N mice transgenic for HER-2/neu, a mammary-tumour model. Treated animals showed a 13.5% increase in mean and 13.9% in maximum lifespan, a 34.2% longer mean lifespan among animals free of neoplasms, a 3.7-fold increase in the number of mice developing no mammary tumours, and fewer lung metastases and multiple tumours. The limits are structural: one strain, one sex, one transgenic background, and the mechanism the authors propose — suppression of HER-2/neu expression — is stated as probable rather than demonstrated in this report.

4. 4.
   in vitroBull Exp Biol Med (2003)

   The primary telomerase report, and a very short one. In telomerase-negative human fetal fibroblast culture, addition of the peptide induced expression of the catalytic subunit, enzymatic activity of telomerase and telomere elongation. It is a brief communication in a single cell type, with no replication described in the abstract, and the conclusion it draws — the possibility of prolonging the life span of a cell population and of the whole organism — is the authors' extrapolation, not something the experiment measured.

Used in research on