Epithalon (also referenced as Epitalon, Epithalone, or Epithalamin in portions of the scientific literature) is a synthetic tetrapeptide with the primary sequence Ala-Glu-Asp-Gly. It is used as a laboratory reagent in experimental models investigating telomere-associated enzymology, peptide–nucleic acid interactions, transcriptional regulation, and circadian-linked signaling networks. Published studies include cell-based experiments and in-vivo animal work assessing molecular endpoints such as telomerase-associated activity, gene expression patterns, and pathway-level biomarkers under controlled study conditions.

The cited literature includes investigations spanning insects, rodents, and non-human primates, as well as cellular systems used to quantify genome stability metrics and transcriptional responses following exposure to short regulatory peptides.

Source: PubChem

Sequence: Ala-Glu-Asp-Gly
Molecular Formula: C14H22N4O9
Molecular Weight: 390.349 g/mol
PubChem CID: 219042
CAS Number: 307297-39-8

• Telomere biology and telomerase-associated enzymology: experimental systems measuring telomerase-associated activity, telomere length metrics, and downstream genome integrity endpoints in cell-based models.
• Peptide–DNA interaction studies: research evaluating interactions of short peptides with promoter regions and associated transcriptional modulation in cultured cells.
• Transcriptional regulation and gene-expression profiling: assays quantifying changes in expression for defined targets implicated in signaling, extracellular matrix biology, and protein biogenesis pathways.
• Circadian-linked molecular signaling: studies assessing transcriptional targets associated with rhythmic regulation and pineal-linked pathways, including AANAT and pCREB-associated signaling nodes.
• Extracellular matrix pathway research: fibroblast and connective-tissue model systems evaluating MMP2-linked endpoints and matrix remodeling biomarkers under controlled conditions.
• Oncology model endpoints: exploratory rodent tumor and transgenic model studies evaluating tumor-associated metrics and molecular correlates as research outcomes.
• Retinal model readouts: rodent retinal degeneration models evaluating structural and electrophysiologic endpoints as experimental measures.

Mechanistic work in the cited literature places epithalon within several experimentally tractable molecular contexts. Cell-based studies describe telomerase-associated activity and telomere-length endpoints following exposure to the tetrapeptide, supporting its use as a tool compound in telomere maintenance research [2].

Additional studies describe short peptide interactions with gene promoter sites (e.g., CD5, IL-2, MMP2, Tram1) as a model framework for evaluating peptide-mediated transcriptional modulation in cell culture systems [5]. In these models, endpoints commonly include promoter interaction assays, transcriptional output (mRNA/protein), and pathway-level markers linked to the targeted loci.

In circadian-associated research contexts, the literature also describes transcriptional targets related to pineal-linked signaling cascades, including arylalkylamine-N-acetyltransferase (AANAT) and pCREB-associated transcriptional signaling, which are evaluated in rhythmic gene regulation paradigms [15].

The following are reported DNA / transcriptional targets or molecular endpoints associated with epithalon in the cited literature:

1. CD5 – promoter-target modeling for immune-cell lineage signaling studies
2. IL-2 – promoter-target modeling for cytokine-associated transcriptional studies
3. MMP2 – extracellular matrix remodeling pathway target used in fibroblast/ECM research models
4. Tram1 – protein biogenesis/translocation-associated target used in transcriptional modeling
5. Arylalkylamine-N-acetyltransferase – pineal/circadian-associated transcriptional target
6. pCREB t – transcriptional signaling node used in circadian-associated research models
7. Telomerase – enzyme activity endpoint used in telomere biology and genome stability studies

1. Telomere-Associated Enzymology and Genome Integrity Readouts

Preclinical investigations include insect and rodent studies evaluating survival curves and biomarker panels under defined experimental conditions [1]. Additional rodent work reports age-associated biomarker panels and tumor-incidence endpoints as measured outcomes in specified strains and study designs [4]. Separate cell-based studies describe telomerase-associated activity and telomere-length metrics as experimental readouts [2].

2. Promoter-Interaction Modeling and Gene-Expression Endpoints

Cell culture studies have described short peptide interactions with promoter regions of selected genes as an experimental framework for transcriptional modulation and gene-expression profiling [5]. Additional rodent work reports interferon-gamma expression as a measured molecular endpoint in aging lymphocyte models under controlled experimental conditions [6].

3. Fibroblast Function and Extracellular Matrix Pathway Biomarkers

The cited literature includes rodent and in vitro studies evaluating fibroblast functional state and extracellular matrix-associated endpoints, including MMP2-linked readouts and apoptosis-pathway markers such as caspase-3 activity in cultured fibroblast systems [7] [8].

4. Tumor-Model Endpoints in Rodent and Transgenic Systems

Multiple studies evaluate tumor-associated endpoints in rodent and transgenic models under defined illumination regimes or genetic backgrounds, including tumor development metrics and metastasis-related observations as experimental outcomes [9] [10] [11] [12] [13].

Slowed tumor growth in mice exposed to epithalon compared to controls
Source: Wiley Online Library

Mechanistic literature also evaluates circadian gene regulation in oncology-related cell systems, including PER1-associated signaling as a node linked to cell-cycle control and DNA damage response pathways in experimental models [14].

PER1 Causes Increased Rates of Ionizing Radiation-Induced Cell Death
Source: Molecular Cell

5. Pineal-Linked Transcriptional Targets and Rhythmic Signaling Readouts

Studies describe regulatory peptide effects on gene transcription, including attention to AANAT and pCREB-associated signaling as targets evaluated in rhythmic gene-expression paradigms [15]. The referenced literature also includes investigations in non-human primates evaluating daily secretion rhythm profiles as measured endpoints under specified study designs [16].

6. Retinal Model Endpoints

The referenced literature includes rodent retinal degeneration models evaluating retina structural condition and electrophysiologic function as experimental endpoints under controlled conditions [17].

Epithalon is a synthetic tetrapeptide (Ala-Glu-Asp-Gly) supplied as a research material for controlled laboratory workflows. For experimental planning and materials qualification, laboratories commonly verify peptide identity and assess analytical attributes using characterization approaches appropriate for peptide materials, in alignment with internal method requirements and study protocols.

Researchers may reference the registry identifiers and structural information in the Biochemical Characteristics section (sequence, molecular formula, molecular weight, PubChem CID, and CAS number) when preparing internal documentation.

The above literature was researched, edited and organized by Dr. Logan, M.D. Dr. Logan holds a doctorate degree from Case Western Reserve University School of Medicine and a B.S. in molecular biology.

Vladimir Khavinson is a Professor, President of the European region of the International Association of Gerontology and Geriatrics; Member of the Russian and Ukrainian Academies of Medical Sciences; Main gerontologist of the Health Committee of the Government of Saint Petersburg, Russia; Director of the Saint Petersburg Institute of Bioregulation and Gerontology; Vice-president of Gerontological Society of the Russian Academy of Sciences; Head of the Chair of Gerontology and Geriatrics of the North-Western State Medical University, St-Petersburg; Colonel of medical service (USSR, Russia), retired. Vladimir Khavinson is known for the discovery, experimental and clinical studies of new classes of peptide bioregulators as well as for the development of bioregulating peptide therapy. He is engaged in studying of the role of peptides in regulation of the mechanisms of ageing. His main field of actions is design, pre-clinical and clinical studies of new peptide geroprotectors. A 40-year-long investigation resulted in a multitude of methods of application of peptide bioregulators to slow down the process of ageing and increase human life span. Six peptide-based pharmaceuticals and 64 peptide food supplements have been introduced into clinical practice by V. Khavinson. He is an author of 196 patents (Russian and international) as well as of 775 scientific publications. His major achievements are presented in two books: “Peptides and Ageing” (NEL, 2002) and “Gerontological aspects of genome peptide regulation” (Karger AG, 2005). Vladimir Khavinson introduced scientific specialty “Gerontology and Geriatrics” in the Russian Federation on the governmental level. Academic Council headed by V. Khavinson has oversighted over 200 Ph.D. and Doctorate theses from many different countries.

Prof. Vladimir Khavinson is being referenced as one of the leading scientists involved in the research and development of Epitalon. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Peptide Sciences and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide. Prof. Vladimir Khavinson is listed in [1] [2] [5] [6] [7] [9] [12] [13] [15] and [17] under the referenced citations.

1. V. N. Anisimov, S. V. Mylnikov, and V. K. Khavinson, “Pineal peptide preparation epithalamin increases the lifespan of fruit flies, mice and rats,” Mech. Ageing Dev., vol. 103, no. 2, pp. 123–132, Jun. 1998. [PubMed]
2. V. K. Khavinson, I. E. Bondarev, and A. A. Butyugov, “Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells,” Bull. Exp. Biol. Med., vol. 135, no. 6, pp. 590–592, Jun. 2003. [PubMed]
3. T. A. Dzhokhadze, T. Z. Buadze, M. N. Gaiozishvili, M. A. Rogava, and T. A. Lazhava, “[Functional regulation of genome with peptide bioregulators by hypertrophic cardiomyopathy (by patients and relatives)],” Georgian Med. News, no. 225, pp. 94–97, Dec. 2013. [PubMed]
4. V. N. Anisimov et al., “Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice,” Biogerontology, vol. 4, no. 4, pp. 193–202, 2003. [PubMed]
5. V. K. Khavinson, S. I. Tarnovskaya, N. S. Linkova, V. E. Pronyaeva, L. K. Shataeva, and P. P. Yakutseni, “Short cell-penetrating peptides: a model of interactions with gene promoter sites,” Bull. Exp. Biol. Med., vol. 154, no. 3, pp. 403–410, Jan. 2013. [PubMed]
6. N. S. Lin’kova, B. I. Kuznik, and V. K. Khavinson, “[Peptide Ala-Glu-Asp-Gly and interferon gamma: their role in immune response during aging],” Adv. Gerontol. Uspekhi Gerontol., vol. 25, no. 3, pp. 478–482, 2012. [PubMed]
7. N. I. Chalisova, N. S. Lin’kova, A. N. Zhekalov, A. O. Orlova, G. A. Ryzhak, and V. K. Khavinson, “[Short peptides stimulate skin cell regeneration during ageing],” Adv. Gerontol. Uspekhi Gerontol., vol. 27, no. 4, pp. 699–703, 2014. [PubMed]
8. N. S. Lin’kova et al., “Peptide Regulation of Skin Fibroblast Functions during Their Aging In Vitro,” Bull. Exp. Biol. Med., vol. 161, no. 1, pp. 175–178, May 2016. [PubMed]
9. I. A. Vinogradova, A. V. Bukalev, M. A. Zabezhinski, A. V. Semenchenko, V. K. Khavinson, and V. N. Anisimov, “Effect of Ala-Glu-Asp-Gly peptide on life span and development of spontaneous tumors in female rats exposed to different illumination regimes,” Bull. Exp. Biol. Med., vol. 144, no. 6, pp. 825–830, Dec. 2007. [PubMed]
10. G. Kossoy, V. N. Anisimov, H. Ben-Hur, N. Kossoy, and I. Zusman, “Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice,” Vivo Athens Greece, vol. 20, no. 2, pp. 253–257, Apr. 2006. [PubMed]
11. V. N. Anisimov et al., “Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER-2/neu transgenic mice,” Int. J. Cancer, vol. 101, no. 1, pp. 7–10, 2002. [PubMed]
12. V. N. Anisimov, V. K. Khavinson, I. N. Alimova, A. V. Semchenko, and A. I. Yashin, “Epithalon decelerates aging and suppresses development of breast adenocarcinomas in transgenic her-2/neu mice,” Bull. Exp. Biol. Med., vol. 134, no. 2, pp. 187–190, Aug. 2002. [PubMed]
13. I. A. Vinogradova, A. V. Bukalev, M. A. Zabezhinski, A. V. Semenchenko, V. K. Khavinson, and V. N. Anisimov, “Geroprotective effect of ala-glu-asp-gly peptide in male rats exposed to different illumination regimens,” Bull. Exp. Biol. Med., vol. 145, no. 4, pp. 472–477, Apr. 2008. [PubMed]
14. S. Gery, N. Komatsu, L. Baldjyan, A. Yu, D. Koo, and H. P. Koeffler, “The circadian gene per1 plays an important role in cell growth and DNA damage control in human cancer cells,” Mol. Cell, vol. 22, no. 3, pp. 375–382, May 2006. [PubMed]
15. V. K. Khavinson, L. K. Shataeva, and A. A. Chernova, “Effect of regulatory peptides on gene transcription,” Bull. Exp. Biol. Med., vol. 136, no. 3, pp. 288–290, Sep. 2003. [PubMed]
16. O. V. Korkushko et al., “[Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people],” Adv. Gerontol. Uspekhi Gerontol., vol. 20, no. 1, pp. 74–85, 2007. [PubMed]
17. V. Khavinson, M. Razumovsky, S. Trofimova, R. Grigorian, and A. Razumovskaya, “Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa,” Neuro Endocrinol. Lett., vol. 23, no. 4, pp. 365–368, Aug. 2002. [PubMed]

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