Epitalon — Molecular Weight, Sequence & Research Evidence Reference

01What is Epitalon?

Epitalon — also written Epithalon — is a four-residue peptide with the sequence AEDG, molecular formula C14H22N4O9 and a molecular weight of 390.35 g/mol. At four amino acids it is the smallest compound in this database. Its chemical characterisation is straightforward and well supported.

The compound is routinely confused with Epithalamin, and the two are not the same substance. Epithalamin is a peptide extract of bovine pineal gland; Epitalon is a defined synthetic tetrapeptide developed as a putative active fragment of it. Much of the older literature attributed to "Epitalon" was in fact performed with the extract, and PubChem's own record compounds the problem by listing Epithalamin as a synonym. Studies should be checked at source for which material was actually used.

The claims most associated with Epitalon — telomerase activation, telomere elongation, extended lifespan — trace to a small number of Russian research groups and rest largely on in vitro work and rodent studies that have not been independently replicated at scale. There are no registered Western clinical trials. This record presents the chemistry as established and the biology as unsettled, because that is what the sources support.

02Molecular information

03Amino acid sequence

Structural modifications

None. Epitalon is an unmodified linear L-amino-acid tetrapeptide with a free N-terminal alpha-amino group and a free C-terminal carboxyl (glycine). Standard alpha-peptide bonds throughout — the 2025 IJMS review notes explicitly that the Glu and Asp residues are linked through their alpha-carboxyl groups rather than side chains, which distinguishes the standard form from possible isopeptide isomers [1]. No acylation, no amidation, no non-natural residues, no disulfide bonds (no cysteine present), no cyclisation, no PEGylation. The review also notes that eight stereoisomers are theoretically possible and that molecular-dynamics work describes two intramolecular salt bridges as structure-stabilising [1].

04Pharmacokinetic information

Half-life context

No pharmacokinetic half-life for Epitalon has been established in any species by any route in the retrieved peer-reviewed literature. The 2025 IJMS review, which surveys roughly 25 years of Epitalon research, contains no pharmacokinetic parameters at all — no bioavailability, no serum half-life, no tissue distribution kinetics, no clearance — and the review itself flags the scarcity of physicochemical and structural work on the peptide as a gap [1]. Published animal and human studies dosed by intramuscular injection, parabulbar injection, intranasal, and sublingual routes without accompanying PK characterisation [1][6]. Any specific half-life figure circulating for Epitalon (commonly quoted vendor values in the range of minutes to a few hours) has no traceable primary source in the literature retrieved here and should be treated as unsupported. Mechanistically, an unprotected linear tetrapeptide with free termini would be expected to be rapidly cleared by plasma and tissue peptidases, but this is an inference from peptide chemistry generally, not a measured value for Epitalon. Reported biological effects in animal studies persist far longer than any plausible plasma residence time, which means effect duration and plasma kinetics cannot be equated for this compound; the mechanism for that dissociation is not established.

05Research focus

Primary research areas

• telomerase activity and telomere length in cell culture
• pineal/melatonin and circadian gene expression
• rodent lifespan and spontaneous tumour incidence
• retinal degeneration models
• antioxidant and antimutagenic effects
• gerontology bioregulator peptide research

Research context

Epitalon is a synthetic tetrapeptide, Ala-Glu-Asp-Gly (AEDG), designed on the basis of the amino-acid composition of Epithalamin, a bovine pineal-gland polypeptide extract [1]. It was developed in Russia by the group of V.Kh. Khavinson, associated with the St Petersburg Institute of Bioregulation and Gerontology, and a Russian synthesis patent was issued in 2001 [1]. Its natural occurrence was not reported until 2017, when it was detected in a physiological pineal extract [1].

The most-cited finding is in vitro. Khavinson and colleagues reported in 2003 that adding Epithalon to telomerase-negative human fetal fibroblast cultures induced expression of the telomerase catalytic subunit, enzymatic telomerase activity, and telomere elongation, which the authors interpreted as reactivation of the telomerase gene in somatic cells [2]. In 2025 an independent UK group at Brunel University London reported a broader in vitro study: Epitalon at 0.1-1.0 micrograms/mL produced dose-dependent telomere elongation in breast cancer lines, normal fibroblasts and normal epithelial cells, with hTERT upregulation and telomerase activity in normal cells and activation of alternative lengthening of telomeres in cancer lines [4]. This is currently the clearest non-Russian in vitro replication of the telomere effect; a correction to that paper was published in November 2025.

Animal work has been reported chiefly by the originating group. Anisimov et al. gave Epitalon monthly to female Swiss-derived SHR mice from 3 months of age until death: mean lifespan and overall tumour incidence were unchanged, but the last-10%-survivor lifespan increased 13.3%, maximum lifespan 12.3%, bone-marrow chromosome aberrations fell 17.1%, and leukaemia development was reduced 6-fold [3]. Human reports are limited to two small studies described in the 2025 review: a retinitis pigmentosa series (162 patients, parabulbar injection) and a placebo-controlled circadian/melatonin study in 75 women using sublingual administration [1]. Neither is a registered Western trial.

06Research evidence and limitations

Regulatory status

Not an approved drug in the United States, the European Union, or any Western jurisdiction. Epitalon has no FDA approval, no EMA marketing authorisation, and no registered Western clinical trials were identified. The related but distinct bovine pineal extract Epithalamin has reportedly been registered in Russia for menopause- and infertility-related indications; this Russian registration applies to the extract, not to the synthetic AEDG tetrapeptide, and does not constitute Western regulatory approval [6]. Compounding status in the United States has recently shifted: epitalon was placed on FDA's list of bulk drug substances that may present significant safety risks (503A Category 2) in October 2023 on immunogenicity grounds, and was among the substances withdrawn from that list in the 22 April 2026 revision, with FDA scheduling Pharmacy Compounding Advisory Committee meetings for July 2026 and before February 2027 to consider whether such peptides should be added to the 503A bulks list [5]. Removal from Category 2 does not by itself authorise compounding — the substance is not on the 503A bulks list. Epitalon is otherwise supplied and sold as a research chemical for laboratory use only, not for human administration.

07Research material and sourcing notes

Reported research-use reconstitution information

Supplier technical documentation only (MedChemExpress datasheet, catalogue HY-P1149): in vitro solubility in water is stated as greater than or equal to 50 mg/mL (128.09 mM). No pH, buffer, or DMSO figure is given on that datasheet. No reconstitution protocol appears in the peer-reviewed literature retrieved, and no manufacturer pharmaceutical product exists in Western markets to supply an authoritative one. Published studies administered aqueous solutions by intramuscular, parabulbar, intranasal or sublingual routes but generally did not specify formulation detail [1]. Treat the 50 mg/mL water solubility as vendor technical data, not as a validated pharmaceutical specification. No dosing guidance is given here.

Reported storage and stability information

Supplier technical documentation only (MedChemExpress datasheet, catalogue HY-P1149). Lyophilised powder: -80°C for up to 2 years, or -20°C for up to 1 year. In solvent: -80°C for up to 6 months, or -20°C for up to 1 month, sealed and protected from moisture and light. No storage stability data from peer-reviewed literature or from a pharmaceutical manufacturer was retrieved. These are supplier-recommended handling conditions for research-grade material, not validated shelf-life specifications.

Identity and sourcing notes

The single most important identity issue is nomenclature. Epitalon (synthetic AEDG tetrapeptide) and Epithalamin (a crude bovine pineal polypeptide extract, a mixture) are distinct substances, and conflating them is endemic — PubChem CID 219042 itself lists 'Epithalamin' and 'Epithalamine' among the depositor-supplied synonyms for the tetrapeptide, which is incorrect and propagates the confusion. Literature attributing effects to 'epithalamin' cannot be assumed to apply to the tetrapeptide, and the ADDF assessment notes that because Epithalamin is a polypeptide mixture it is difficult to determine which effects are attributable to the tetrapeptide alone [6]. 'Epithalon', 'Epithalone' and 'AEDG peptide' all refer to the same tetrapeptide. Analytical identity for a 4-mer is not trivial: mass alone cannot distinguish sequence permutations or alpha- versus isopeptide linkage isomers at the Glu and Asp residues, so LC-MS/MS sequencing plus amino-acid analysis is preferable to HPLC purity plus nominal mass. Vanhee et al. published an LC-MS/MS characterisation of Epitalon in two illegal pharmaceutical preparations seized by Belgian authorities, demonstrating that grey-market Epitalon products are a documented analytical subject in their own right [5-adjacent, see reference 5]. Certificates of analysis should state salt form (acetate versus TFA), net peptide content, and the analytical method used for identity. This is informational, not promotional.

08References and evidence

Primary sources

1. Overview of Epitalon — Highly Bioactive Pineal Tetrapeptide with Promising PropertiesreviewAraj SK, Brzezik J, Mądra-Gackowska K, Szeleszczuk Ł — International Journal of Molecular Sciences, 2025;26(6):2691
2. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cellsprimary literatureKhavinson VKh, Bondarev IE, Butyugov AA — Bulletin of Experimental Biology and Medicine, 2003;135(6):590-592
3. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR miceprimary literatureAnisimov VN, Khavinson VKh, Popovich IG, Zabezhinski MA, Alimova IN, Rosenfeld SV, Zavarzina NYu, Semenchenko AV, Yashin AI — Biogerontology, 2003;4(4):193-202
4. Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activityprimary literatureAl-Dulaimi S, Thomas R, Matta S, Roberts T — Biogerontology, 2025;26:178 (correction: Biogerontology 2025, doi:10.1007/s10522-025-10326-8)
5. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (503A Category 2 list; epitalon listed among withdrawn substances as of the 22 April 2026 revision)regulatoryUS Food and Drug Administration — US FDA, page last updated 22 April 2026
6. Epithalamin/Epithalon — Cognitive Vitality Report for ResearchersreviewAlzheimer's Drug Discovery Foundation — Alzheimer's Drug Discovery Foundation, Cognitive Vitality Reports

Chemical and molecular databases

• PubChem CID 219042 (Epitalon) — C14H22N4O9, 390.35 g/mol, UNII O65P17785G, CAS 307297-39-8 and 64082-79-7
• MedChemExpress technical datasheet HY-P1149 (Epitalon) — MW 390.35, water solubility ≥50 mg/mL, storage conditions (supplier technical documentation)
• Vanhee C, Moens G, et al. 'Identification of the small research tetra peptide Epitalon... in two illegal pharmaceutical preparations', Drug Testing and Analysis, 2015, doi:10.1002/dta.1771 — grey-market product analytical characterisation
• Correction notice for Al-Dulaimi et al. 2025 (PMID 41240216)

09Related compounds

• ThymalinAnother Khavinson-group peptide bioregulator derived from an animal-tissue extract (thymus rather than pineal), developed under the same Russian research programme and carrying the same evidence-provenance caveats.Reference page in preparation
• Thymosin Alpha-1A thymic peptide often discussed alongside Epitalon in the pineal-thymic neuroendocrine ageing literature, but with a far more developed Western evidence base — a useful contrast in evidence quality.Reference page in preparation
• MOTS-cThe other compound in this set marketed as a longevity peptide; both are short endogenous-derived peptides with strong preclinical claims and no established human pharmacokinetics.
• HumaninA short endogenous peptide studied for cytoprotective and ageing-related effects, frequently grouped with Epitalon in geroprotective-peptide literature despite a different origin (mitochondrial-derived).Reference page in preparation
• DSIPDelta sleep-inducing peptide is another short peptide whose literature originates largely from Eastern European groups and which is studied for pineal/circadian and neuroendocrine effects, making the sourcing and replication issues directly comparable.Reference page in preparation

10Frequently asked questions