Khavinson Peptide Bioregulators — GenoPept research guide (research use only)

Khavinson Peptide Bioregulators: The Complete Research Guide (Vilon, Epitalon, Thymalin, Pinealon, Cortagen, Cardiogen and more)

Peptide bioregulators are very short peptides — two to four amino acids — developed largely in St Petersburg under Professor Vladimir Khavinson and studied as tissue-specific regulators of gene expression. This guide maps the whole Khavinson family, gives the sequence of every bioregulator GenoPept stocks, explains the cytomax versus cytogen distinction, and gives an unvarnished assessment of an evidence base that is far thinner than its popular reputation suggests. Research context only.

Updated ~14 min readReviewed by the GenoPept technical team

Key takeaways

  • Peptide bioregulators are di-, tri- and tetrapeptides — most under 550 Da — each associated in the literature with a specific tissue or organ system.
  • The family splits in two: cytomaxes are natural organ extracts (Thymalin, Epithalamin); cytogens are chemically defined synthetic short peptides (Vilon, Epitalon, Pinealon and the rest).
  • The mechanistic hypothesis is that these peptides enter the nucleus and interact directly with promoter DNA and histones — an idea set out in the Khavinson group’s own 2021 Molecules systematic review.
  • Sixteen bioregulators are stocked, from the dipeptide Vilon (Lys-Glu) to the tetrapeptide Pancragen (Lys-Glu-Asp-Trp); all sequences are tabulated below.
  • Evidence quality is the honest problem: most studies are small, from the originating network, frequently Russian-language, and rarely replicated independently.
  • Some peptides (Epitalon, Vilon, Pancragen, Bronchogen) have gene-expression data in indexed journals; others are supported almost entirely by developers’ monographs.
  • Every bioregulator here is supplied lyophilised with a per-batch third-party certificate of analysis, for laboratory research only.

What are peptide bioregulators?

Peptide bioregulators are ultra-short peptides — usually two to four residues — proposed to act as tissue-specific regulators of gene transcription rather than as receptor ligands. The concept and most of the primary literature come from the St Petersburg Institute of Bioregulation and Gerontology, where Vladimir Khavinson’s group has worked on them since the 1970s.

The programme began with organ extracts. Investigators fractionated peptide material from calf thymus, pineal gland, cortex, prostate and other tissues and reported tissue-selective biological activity. Over the following decades they identified candidate short sequences within those fractions and synthesised them as defined peptides.

The result is a catalogue of named compounds — Vilon, Epitalon, Pinealon, Cortagen, Cardiogen, Vesugen, Pancragen and others — each built from the same small alphabet of residues, dominated by lysine, glutamate, aspartate and one variable residue that the developers associate with tissue selectivity.

These are not conventional signalling peptides. They have no known cell-surface receptor, no established pharmacokinetic profile in the peer-reviewed literature, and their proposed mechanism sits outside standard receptor pharmacology. That makes them scientifically interesting and, equally, hard to evaluate.

Cytomaxes vs cytogens: two different kinds of product

Cytomaxes are natural peptide extracts from animal organs; cytogens are chemically defined synthetic short peptides. Conflating the two is the single most common error in writing about this family. A study on a cytomax is not evidence about a cytogen, even when the two are marketed as counterparts.

Thymalin is a cytomax: a polypeptide complex isolated from calf thymus, not a single defined molecule. Epithalamin, the pineal extract, is another. Both are mixtures whose exact composition varies with the preparation.

Epitalon (Ala-Glu-Asp-Gly) is a cytogen: one synthetic tetrapeptide, one CAS number, one molecular weight, verifiable by HPLC and mass spectrometry. So are Vilon, Pinealon, Cortagen and every other named short peptide in the table below.

This distinction has real consequences for citation. The best-known human-cohort publication in this field — Khavinson and Morozov’s 2003 report following 266 older participants over six to eight years and describing reduced mortality — used Thymalin and Epithalamin, the extracts. It is routinely cited as though it were evidence for the synthetic tetrapeptides. It is not.

Diagram of the peptide bioregulator hypothesis: a short peptide entering the cell nucleus and interacting with promoter DNA to alter gene expression The bioregulator hypothesis (as proposed by its developers) Short peptide 2–4 residues < 550 Da Cell membrane Passive entry proposed no known receptor Nucleus Nuclear entry reported in vitro Promoter DNA and histone binding structural data limited Altered transcription of tissue-specific genes e.g. PDX1 / NGN3 (Pancragen), p16 / p21 (Vesugen) Status of this model Hypothesis, largely from one research network Independent confirmation of direct peptide–DNA binding at physiological concentrations remains limited.
Figure 1. The proposed mechanism for peptide bioregulators — short peptide to nucleus to gene expression — with the points where evidence is weakest marked in amber.

The proposed mechanism: short peptides and gene expression

The unifying claim of the bioregulator field is that peptides of two to four residues can cross the cell and nuclear membranes and bind directly to regulatory DNA sequences, changing which genes a tissue transcribes. The Khavinson group set this out most fully in a 2021 systematic review in Molecules.

That review catalogues specific peptide–gene associations, and it is the most useful single entry point to the primary literature. Examples it lists include Pancragen (Lys-Glu-Asp-Trp) and pancreatic endocrine differentiation genes PDX1, NGN3 and PAX6; Vesugen (Lys-Glu-Asp) and senescence markers p16 and p21; Bronchogen (Ala-Glu-Asp-Leu) and bronchial epithelial genes including MUC family members and SFTPA1; and Pinealon (Glu-Asp-Arg) and Fkbp1b in neurons.

Why the model is contested

Three problems recur. First, direct sequence-specific binding of a dipeptide or tetrapeptide to double-stranded DNA is chemically demanding — such a short ligand has limited surface with which to read a base sequence. Second, most of the supporting biophysics comes from the same network that proposed the model. Third, cellular uptake and nuclear delivery of small, highly charged peptides is not straightforward and is rarely quantified in these papers.

None of that makes the observations wrong. It does mean the mechanism should be described as a working hypothesis, and effects should be reported as observed changes in gene expression rather than as demonstrated direct DNA binding.

Every Khavinson bioregulator in the store, with sequences

All sixteen bioregulators stocked are listed below with their one-letter and three-letter sequences, the tissue each is associated with in the literature, and a direct product link. Fourteen are defined synthetic short peptides; Thymalin is an extract, and Epitalon has its own dedicated guide.

Table 1. Khavinson peptide bioregulators stocked at GenoPept — names, sequences and tissue focus
BioregulatorSequence (1-letter)Sequence (3-letter)LengthTissue / system in the literatureType
VilonKELys-GluDipeptideThymus and immune functionCytogen
EpitalonAEDGAla-Glu-Asp-GlyTetrapeptidePineal gland, neuroendocrine, telomere biologyCytogen
PinealonEDRGlu-Asp-ArgTripeptideNeurons, neuroprotection modelsCytogen
VesugenKEDLys-Glu-AspTripeptideVascular endothelium, senescence markersCytogen
CartalaxAEDAla-Glu-AspTripeptideCartilage and connective tissue, skin fibroblastsCytogen
BronchogenAEDLAla-Glu-Asp-LeuTetrapeptideBronchial epithelium, lungCytogen
ChonlutenEDGGlu-Asp-GlyTripeptideRespiratory and gastric mucosaCytogen
CardiogenAEDRAla-Glu-Asp-ArgTetrapeptideCardiovascular system, myocardiumCytogen
CortagenAEDPAla-Glu-Asp-ProTetrapeptideCerebral cortex, peripheral nerveCytogen
CrystagenEDPGlu-Asp-ProTripeptideImmune system, thymic functionCytogen
LivagenKEDALys-Glu-Asp-AlaTetrapeptideLiver; chromatin studies in lymphocytesCytogen
OvagenEDLGlu-Asp-LeuTripeptideHepatic and renal cell functionCytogen
PancragenKEDWLys-Glu-Asp-TrpTetrapeptidePancreatic endocrine cells (PDX1, NGN3, PAX6)Cytogen
ProstamaxKEDPLys-Glu-Asp-ProTetrapeptideProstate tissueCytogen
TestagenKEDGLys-Glu-Asp-GlyTetrapeptideMale reproductive tissueCytogen
ThymalinPolypeptide complex (not a single sequence)ExtractThymus, immune regulationCytomax
Reading the table. Sequences for Vilon, Epitalon, Pinealon, Vesugen, Cartalax, Bronchogen, Ovagen, Testagen, Pancragen and Cardiogen appear with these gene associations in the Khavinson group’s 2021 Molecules review. Chonluten, Cortagen, Crystagen, Livagen and Prostamax are documented mainly in the developers’ monographs and Russian-language reports; treat tissue attributions for those as weaker.

Which bioregulator maps to which tissue

The organising idea of the family is one peptide per tissue: each bioregulator is named for, and studied in, a particular organ system. Grouping them by system is the fastest way to navigate the catalogue and to see where several compounds overlap.

Organ system map linking every Khavinson peptide bioregulator to the tissue it is studied in, with amino-acid sequences Peptide bioregulators by organ system Sequence shown in one-letter code · blue = defined synthetic peptide · amber = organ extract Immune / thymus Vilon — KE Crystagen — EDP Thymalin — extract Pineal / neuroendocrine Epitalon — AEDG Telomerase and melatonin rhythm research Brain / nervous system Pinealon — EDR Cortagen — AEDP Neuroprotection models Heart / vasculature Cardiogen — AEDR Vesugen — KED p16 / p21 senescence work Lung / airway Bronchogen — AEDL Chonluten — EDG MUC genes, SFTPA1 Liver / kidney Livagen — KEDA Ovagen — EDL Chromatin decondensation Pancreas Pancragen — KEDW PDX1, NGN3, PAX6 endocrine differentiation Reproductive tissue Testagen — KEDG Prostamax — KEDP Developers’ monographs Cartilage / connective Cartalax — AED Chondrocyte and skin fibroblast culturesGene names shown are those reported in the Khavinson group’s 2021 systematic review; not all attributions carry equal evidence.
Figure 2. Organ map of the Khavinson peptide bioregulators, linking every stocked compound and its sequence to the tissue system it is studied in.

Two patterns are worth noticing. Nearly every sequence is built from Lys, Glu and Asp plus one variable residue — Trp in Pancragen, Leu in Bronchogen and Ovagen, Pro in Cortagen, Crystagen and Prostamax. And several systems have more than one assigned peptide, which is why comparative work within a system is more informative than comparing across systems.

How good is the evidence, really?

The bioregulator literature is broad but shallow: many publications, mostly small, mostly from one research network, mostly in Russian-language or low-circulation journals, and rarely replicated by independent laboratories. That is the fair summary, and it should be stated plainly whenever these compounds are cited.

The strongest indexed material is the gene-expression work. The 2021 Molecules systematic review compiles peptide-to-gene associations across the family and is peer-reviewed in an indexed journal — although it is authored by the group that developed the compounds.

Animal work is more mixed than its reputation suggests. Anisimov and Khavinson’s 2010 Biogerontology review reports that long-term treatment with some peptide preparations increased mean lifespan by 20–40% in rodents. But look at an individual study: the 2003 SHR mouse experiment with Epitalon found no change in mean lifespan, a 12.3% increase in maximum lifespan, roughly 17% fewer chromosome aberrations and a six-fold drop in leukaemia incidence with total tumour incidence unchanged. Aggregate review statements and individual primary results do not always line up.

A 2025 review of Epitalon in the International Journal of Molecular Sciences, written by authors outside the originating group, was broadly positive about the biological activity literature while stating that physico-chemical and structural investigation of the peptide remains quite limited and that the described mechanisms may not be the only ones operating.

Table 2. Evidence tiers across the bioregulator family
TierWhat existsExamplesHow to cite it
Indexed gene-expression dataCell-culture studies with named target genes, compiled in a peer-reviewed systematic reviewPancragen, Bronchogen, Vesugen, Pinealon, Epitalon“Reported to modulate expression of X in cell culture”
Rodent biomarker and lifespan studiesSingle-group experiments with mixed endpoints; effects on maximum rather than mean lifespanEpitalon, Vilon, Thymalin“In one rodent study, X was reported…”
Human cohort reportsLong observation periods, non-blinded, single centre — and usually using extracts, not synthetic peptidesThymalin, Epithalamin (extracts)Name the preparation used; never generalise to cytogens
Developers’ monographs onlyTissue attribution described but little indexed primary dataCortagen, Crystagen, Livagen, Prostamax, Chonluten“Described by its developers as…”
Independent replicationSparse across the entire familyState the absence explicitly
Publication caution. A large share of this field appears in journals with limited international indexing, frequently without blinding, randomisation detail or pre-registration, and often authored by the same group. None of that proves the findings wrong — it means independent replication is the missing ingredient, and any write-up should say so.

Laboratory handling and solution preparation

Short bioregulator peptides are highly polar, dissolve readily in water, and are chemically simpler to handle than most research peptides — none of the common sequences contains methionine or cysteine, so oxidation is not the leading degradation route. The main practical risks are moisture ingress into the lyophilised cake and freeze-thaw damage to solutions.

Comparison chart of cytomax organ extracts versus cytogen synthetic short peptides for peptide bioregulators Cytomax vs cytogen — what you can verify Cytomax (extract) Example: Thymalin, Epithalamin Source: animal organ fraction Composition: mixture, batch-variable Single MW: no MS identity check: not meaningful QC: protein/peptide content assay Most human-cohort reports used these Cytogen (synthetic) Example: Vilon KE, Epitalon AEDG Source: solid-phase synthesis Composition: one defined sequence Single MW: yes MS identity check: yes QC: RP-HPLC purity + ESI-MS Most gene-expression work used these
Figure 3. Cytomax extracts versus cytogen synthetic peptide bioregulators, and what each type of material allows a certificate of analysis to confirm.
  1. Warm before opening. Bring the sealed vial to room temperature so moisture does not condense onto a cold cake.
  2. Add diluent gently. Run sterile or bacteriostatic water down the inside wall of the vial; swirl until clear, never shake.
  3. Confirm clarity. Bioregulator solutions should be clear and colourless with no particulates.
  4. Aliquot single uses. Split the stock so no vial is thawed twice.
  5. Record everything. Compound, sequence, batch, concentration, diluent and date on each aliquot.
Table 3. Concentration reference for solution preparation, 20 mg bioregulator vials
Diluent addedResulting concentrationAmount per 0.1 mLAmount per 0.5 mL
1 mL20 mg/mL2000 mcg10 000 mcg
2 mL10 mg/mL1000 mcg5000 mcg
4 mL5 mg/mL500 mcg2500 mcg
5 mL4 mg/mL400 mcg2000 mcg
10 mL2 mg/mL200 mcg1000 mcg

These figures are a concentration reference for preparing laboratory solutions. Because bioregulators are supplied as salts, molar concentrations calculated from label mass are upper bounds; use net peptide content from the certificate of analysis where molarity matters. Fuller method detail is in the reconstitution guide.

Frequently asked questions

What are peptide bioregulators?

Peptide bioregulators are very short peptides — typically two to four amino acids — developed largely by Vladimir Khavinson’s group in St Petersburg. Each is associated with a specific tissue, and the class hypothesis is that they act inside the nucleus on gene transcription rather than through cell-surface receptors. In research supply they are lyophilised powders handled like any other short synthetic peptide.

What is the difference between a cytomax and a cytogen?

Cytomaxes are peptide extracts prepared from animal organs — Thymalin from calf thymus, Epithalamin from pineal gland. They are mixtures with no single molecular weight. Cytogens are chemically defined synthetic short peptides such as Vilon (Lys-Glu) or Epitalon (Ala-Glu-Asp-Gly), each with one sequence, one CAS number and a verifiable mass spectrum.

What is the sequence of Vilon?

Vilon is the dipeptide Lys-Glu (KE), the shortest member of the family. In the Khavinson group’s 2021 systematic review it is associated with immune function, neuronal differentiation and circadian gene activity in cell-culture work. Because it is only two residues, it is straightforward to synthesise and to verify by mass spectrometry against a certificate of analysis.

Is Thymalin a defined peptide?

No. Thymalin is a polypeptide complex extracted from calf thymus, not a single sequence, so it has no molecular formula or CAS number in the way a synthetic peptide does. That also means mass-spectrometric identity confirmation is not meaningful for it; quality control relies on peptide content assays and process consistency instead.

How strong is the evidence for peptide bioregulators?

Weaker than the popular reputation. Much of the literature consists of small studies from the originating research network, frequently published in Russian-language or low-circulation journals, with little independent replication. Indexed gene-expression data exists for several compounds, and a 2021 systematic review in Molecules compiles it, but that review is authored by the developers themselves.

Do bioregulator peptides really bind DNA directly?

That is the hypothesis proposed by the field’s developers, not an independently established fact. A two- to four-residue peptide has limited surface with which to read a specific DNA sequence, and cellular uptake and nuclear delivery of small charged peptides is rarely quantified in these papers. Describe observed effects as changes in gene expression rather than as demonstrated direct binding.

Which bioregulator has the most published research?

Epitalon (Ala-Glu-Asp-Gly) is the most studied and the only one with a dedicated review by authors outside the originating group — a 2025 paper in the International Journal of Molecular Sciences. Pancragen, Bronchogen, Vesugen and Pinealon follow, each with named target genes reported in cell-culture work compiled in the 2021 Molecules review.

How should bioregulator peptides be stored?

Sealed lyophilised vials are best held frozen at −20 °C for long-term storage, with 2–8 °C acceptable as a working store, kept dry and dark. Once reconstituted, refrigerate and use within a short window or split into single-use aliquots and freeze. None of the common bioregulator sequences contains methionine or cysteine, so oxidation is not the leading degradation route.

References

  1. Khavinson VKh, Popovich IG, Linkova NS, Mironova ES, Ilina AR. Peptide regulation of gene expression: a systematic review. Molecules. 2021;26(22):7053. DOI
  2. Anisimov VN, Khavinson VKh. Peptide bioregulation of aging: results and prospects. Biogerontology. 2010;11(2):139–149. DOI
  3. Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life. Neuroendocrinology Letters. 2003;24(3–4):233–240. Journal page
  4. Khavinson VKh, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bulletin of Experimental Biology and Medicine. 2003;135(6):590–592. DOI
  5. Anisimov VN, Khavinson VKh, Popovich IG, et al. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology. 2003;4(4):193–202. DOI
  6. Araj SK, Brzezik J, Mądra-Gackowska K, Szeleszczuk Ł. Overview of Epitalon — highly bioactive pineal tetrapeptide with promising properties. International Journal of Molecular Sciences. 2025;26(6):2691. DOI

Research-grade peptide bioregulators, batch-verified

GenoPept supplies the full Khavinson bioregulator range as lyophilised vials with a per-batch third-party certificate of analysis covering HPLC purity and mass-spectrometry identity, dispatched from the UK, strictly for laboratory research.

Browse bioregulators See COA certificates

Research use only. All products described on this page are supplied strictly for in-vitro laboratory research and analytical purposes. They are not medicines, are not for human or veterinary use, and must not be used for diagnosis, treatment, cure or prevention of any disease or condition. Nothing on this page is medical, legal or dosing advice. Purchasers must be qualified researchers or institutions and must comply with all applicable laws. See our Research Use Only policy.

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