Peptide Bioregulators
Explained

What are peptide bioregulators?

Peptide bioregulators are organ-derived peptide preparations and short synthetic peptides developed by V. Kh. Khavinson, V. G. Morozov and colleagues, mainly at the St Petersburg Institute of Bioregulation and Gerontology. The group describes two kinds of material: polypeptide complexes extracted from animal organs, and di-, tri- and tetrapeptides synthesized as analogues of them (Anisimov and Khavinson, 2010).

The term is that group's label, not a pharmacological or regulatory category, and it lives mostly in Russian-language journals: of about 100 PubMed records that use the phrase "peptide bioregulator", roughly four in five are Russian-language papers. Disguised Alpha supplies several of these peptides as lyophilized research materials, for laboratory research use only. Nothing on this page is guidance for use in people.

Where the idea came from: organ extracts

The programme began with acid extracts of animal organs. Peptides isolated from calf thymus by mild acid extraction became the preparation thymalin, and a dipeptide separated from it by reversed-phase chromatography, Glu-Trp, became thymogen (Morozov and Khavinson, 1997). The group called such extracts cytomedins and tested them on rat explant cultures, with extracts of brain, heart, liver and thymus active at 5 to 100 ng/mL (Chalisova et al., 2000).

It reported that each extract stimulated explants of its own source tissue: the pineal preparation epithalamin, for example, stimulated pineal explants but not those of other tissues (Khavinson, 2002). Later mass spectrometry of a pineal polypeptide complex found free amino acids and di- to pentapeptides, with tripeptides the largest fraction at about 51 percent, and detected the tetrapeptide Ala-Glu-Asp-Gly among them (Khavinson et al., 2017).

From extracts to short synthetic peptides

From the amino acid composition of the extracts, the group designed short peptides meant to reproduce their tissue-specific activity: dipeptides for the thymus, tetrapeptides for the heart, liver, brain cortex and pineal gland, and one tetrapeptide, Ala-Glu-Asp-Gly, for both the pineal gland and the retina, named epitalon (Khavinson, 2002). The group's 2021 systematic review tabulates the main sequences and the function each is linked to:

Source: Table 5 of Khavinson et al., 2021. The associations are the authors' own and rest mainly on their own studies.

The hypotheses behind the term

Three linked hypotheses run through these papers. The first is tissue specificity: each peptide is proposed to act mainly on the tissue its parent extract came from. In rat explants, four synthetic peptides each stimulated explants of the matching organ at 0.05 ng/mL (Zakutskii et al., 2006), and in human cell cultures three peptides each induced differentiation factors in a different cell type (Khavinson et al., 2012).

The second is a mechanism. Peptides of two to seven residues are proposed to enter the nucleus and bind histones and specific DNA sequences, changing gene expression and DNA methylation (Khavinson et al., 2021). Fluorescence-labeled peptides have been seen in the nucleus of HeLa cells and bind oligonucleotides in a sequence-dependent way (Fedoreyeva et al., 2011), and an independent physics group at St Petersburg State University found pinealon partly entering the DNA major groove (Silanteva et al., 2019).

The group's own review of pinealon still describes cell entry and binding as assumed (Khavinson et al., 2020), and it has also proposed uptake through peptide and amino acid transporters as the basis of tissue specificity (Khavinson et al., 2022).

The third is Khavinson's "peptide theory of ageing": that ageing involves gene-expression changes that reduce synthesis of tissue-specific regulatory peptides, and that supplying such peptides could normalize function (Khavinson, 2002). None of the three has been tested systematically by laboratories outside the programme.

Models used in the research

Organotypic explant cultures from young and old rats are the programme's signature method (Chalisova et al., 2000). Cell work uses thymocytes, fibroblasts, neurons and stem cells, often tracking differentiation (Khavinson et al., 2020) or a few markers of proliferation and apoptosis. Whole-animal work includes rat lifespan and tumor studies: in 76 female rats given thymogen or saline five times a week for 12 months, mean lifespan did not differ, but the longest-lived tenth survived longer and tumors were less frequent (Anisimov et al., 2000).

Molecular docking is used to propose binding sites. The most-cited human report, from the group itself, followed 266 older people in St Petersburg and Kiev for 6 to 8 years and attributed lower mortality to the thymus and pineal extracts (Khavinson and Morozov, 2003).

How strong is the evidence?

By the usual standards, weak. Nearly all of it comes from one institute and its collaborators, much of it in Russian-language journals with short English abstracts. Studies are small, outcomes are often a handful of markers, many papers test several peptides together, and the human reports we reviewed do not describe blinding or placebo control.

One of the few tests run outside St Petersburg was negative: a Paris perifusion study of rat pineal glands, with Khavinson and V. N. Anisimov as co-authors, found that epitalon did not change melatonin secretion at 10⁻⁴ to 10⁻⁶ M (Djeridane et al., 2003). Two of these materials, the thymus extract thymalin and the dipeptide thymogen, are registered medicines in the Russian Federation (Khavinson et al., 2020). None of the bioregulators sold here is an approved drug in the United States.

Bioregulators for sale: what Disguised Alpha carries

Disguised Alpha sells these as lyophilized research materials for laboratory use. They are research chemicals, not dietary supplements, and are not for human consumption.

• Epitalon: Ala-Glu-Asp-Gly. Research guide.
• Pinealon: Glu-Asp-Arg. Research guide.
• Vesugen: Lys-Glu-Asp. Research guide.
• Cardiogen: Ala-Glu-Asp-Arg. Research guide. Its product page lists no certificate at the time of writing; ask support for the certificate covering your lot.
• Cartalax: Ala-Glu-Asp, listed on its product page as C₁₂H₁₉N₃O₈, 333.29 g/mol.
• Thymalin: the calf thymus polypeptide preparation, a mixture rather than one sequence. Research guide.

Certificates for tested lots are published on the product pages and in the COA portal.

Key sources

1. Morozov VG, Khavinson VK. "Natural and synthetic thymic peptides as therapeutics for immune dysfunction." Int J Immunopharmacol. 1997. PMID 9637345. DOI 10.1016/s0192-0561(97)00058-1. The thymus extract and the dipeptides derived from it.
2. Khavinson VKh. "Peptides and Ageing." Neuro Endocrinol Lett. 2002. PMID 12374906. The originating group's account of extracts, designed peptides and its theory.
3. Anisimov VN, Khavinson VKh. "Peptide bioregulation of aging: results and prospects." Biogerontology. 2010. PMID 19830585. DOI 10.1007/s10522-009-9249-8. Review by the originating group.
4. Fedoreyeva LI, et al. "Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNA." Biochemistry (Mosc). 2011. PMID 22117547. DOI 10.1134/S0006297911110022. Cell imaging and binding assays.
5. Silanteva IA, et al. "Role of Mono- and Divalent Ions in Peptide Glu-Asp-Arg-DNA Interaction." J Phys Chem B. 2019. PMID 30762356. DOI 10.1021/acs.jpcb.8b10359. Independent physical chemistry.
6. Djeridane Y, et al. "Effect of a synthetic pineal tetrapeptide (Ala-Glu-Asp-Gly) on melatonin secretion by the pineal gland of young and old rats." J Endocrinol Invest. 2003. PMID 12809170. DOI 10.1007/BF03345159. A negative result.
7. Khavinson VK, et al. "Peptide Regulation of Gene Expression: A Systematic Review." Molecules. 2021. PMID 34834147. DOI 10.3390/molecules26227053. The group's review, with its table of sequences.

Frequently asked questions

What are bioregulators?

In the peptide literature, the organ extracts and short synthetic peptides developed by V. Kh. Khavinson's group in St Petersburg and proposed to act on specific tissues (Anisimov and Khavinson, 2010). The word is that group's label, not a recognized drug class.

Are peptide bioregulators supplements?

Not the materials sold here. Disguised Alpha supplies them as lyophilized research chemicals for laboratory use, not as dietary supplements, and they are not for human consumption.

How strong is the evidence for peptide bioregulators?

Limited: mostly one institute, many Russian-language papers, small studies reading a few markers, and human reports without described blinding or placebo control. One of the few studies run outside St Petersburg found no effect of epitalon on melatonin secretion (Djeridane et al., 2003).

Where can researchers buy peptide bioregulators?

Disguised Alpha carries Epitalon, Pinealon, Vesugen, Cardiogen, Cartalax and Thymalin for laboratory research.

Related links

• Epitalon research guide
• Pinealon research guide
• Cardiogen research guide
• Thymalin research guide
• COA portal: published certificates, by lot
• Research hub

Disguised Alpha products are for research use only. They have not been evaluated for safety or effectiveness in humans. Not for human consumption. All products are intended for laboratory research purposes only.

Research basics

• What is a peptide?
• What is a certificate of analysis (COA)?
• What does lyophilized mean?