Family overview — short-peptide research

Peptide Bioregulators: What the Khavinson Short-Peptide Literature Actually Shows

The peptide bioregulators are a family of very short synthetic peptides — two to four amino acids — that arrive with trade names, assigned target organs and a large body of publications behind them. That body of publications is the problem and the point. It is real, it is indexed, and it is concentrated in one research group to a degree that is unusual in modern biomedicine. This page is the family overview: what the programme is, what its proposed mechanism rests on, what the studies actually measured, and where the evidence stops. It is deliberately critical, because a fair reading of this literature is more useful than an enthusiastic one.

RESEARCH USE ONLY. Cellworks supplies compounds strictly for in-vitro laboratory research. Nothing on this page is a medical, efficacy, or dosing claim, and no product is for human or veterinary use.

Reviewed by Jason Fleming — Biochemistry consultant, Nanyang Technological University, Singapore.Last reviewed: 2026-07-22

What the peptide bioregulators are

Peptide bioregulators — also called ultrashort peptides, short peptides or, in some of the group’s own papers, cytogens — are synthetic di-, tri- and tetrapeptides associated with V. Kh. Khavinson and colleagues at the St Petersburg Institute of Bioregulation and Gerontology. The defining features of the family, as a family, are these: the molecules are extremely small; each is given a trade name and a nominal tissue of interest; and the whole set is presented within a single unifying hypothesis about gene regulation.

The naming is worth pausing on, because it does a lot of persuasive work. Bronchogen sounds like it belongs to the bronchi; Cardiogen to the heart; Pancragen to the pancreas. Those names are assignments made by the developers, not conclusions drawn from an independent literature, and a reader should treat them as labels rather than as findings. Several of them, as the individual pages below note, have essentially no published work in the tissue their name points at.

A 2022 review from the originating group (Khavinson et al., Int J Mol Sci, PMID 35887081) tabulates the family with sequences and assigned designations, and it is the single most useful entry point to the naming, because most other sources circulate the same table without attribution. That table is the source used on this site for the sequence of each compound below, cross-checked against primary papers wherever a primary paper states the sequence directly.

Where the programme came from

The line begins not with synthetic peptides but with tissue extracts. Soviet work from the 1970s onward prepared low-molecular-weight peptide fractions from animal organs — thymus, pineal gland, brain cortex, prostate — under names such as thymalin, epithalamin and cortexin. These were mixtures, not defined molecules.

The synthetic family is what came next: short defined sequences chosen on the basis of amino-acid analysis of those extracts, then made by directed synthesis. The clearest published statement of that method appears in the Cortagen paper by Anisimov, Khavinson and Anisimov (Neuro Endocrinol Lett, 2004, PMID 15159690), which describes the tetrapeptide Ala-Glu-Asp-Pro as “obtained by directed synthesis based on amino acid analysis of natural brain cortex peptide preparation Cortexin.” Epitalon (AEDG) stands in the same relation to epithalamin.

This origin story matters when reading the evidence. An amino-acid composition analysis of a complex extract does not identify which sequence in that extract, if any, carried activity — it constrains the residues available. A tetrapeptide assembled from those residues is a new molecule and inherits nothing from the extract except a rationale. Findings about epithalamin the extract are therefore not findings about Epitalon the tetrapeptide, and the two are frequently conflated in secondary and vendor material.

The family, its sequences and its assigned designations

The table below lists the compounds in this library, with the sequence as tabulated in the 2022 review and the designation the developers assigned. The right-hand column is what this site could verify in indexed literature — and the gap between the second and third columns is the honest story of this family.

Compound	Sequence	Developers’ designation	Indexed primary literature found
Vilon	Lys-Glu (KE)	Immunoprotector	Substantial — rodent lifespan, carcinogenesis, chromatin, cell culture
Epitalon	Ala-Glu-Asp-Gly (AEDG)	Geroprotector	Substantial, plus one independent in-vitro re-examination (2025)
Pinealon	Glu-Asp-Arg (EDR)	Neuroprotector	Thin — cell and rodent models only
Cortagen	Ala-Glu-Asp-Pro (AEDP)	Neuroprotector	Moderate — nerve regeneration, microarray, immune assays
Vesugen	Lys-Glu-Asp (KED)	Vasoprotector	Moderate — cell culture and docking; one uncontrolled human report
Pancragen	Lys-Glu-Asp-Trp (KEDW)	Pancreatic regulator	Moderate — rat and rhesus-monkey models; one small human report
Bronchogen	Ala-Glu-Asp-Leu (AEDL)	Bronchoprotector	Thin, but includes the family’s clearest Khavinson-free work
Cartalax	Ala-Glu-Asp (AED)	Chondroprotector	Thin, and none of it in cartilage
Cardiogen	Ala-Glu-Asp-Arg (AEDR)	Cardioprotector	Thin — two rodent studies; designation traces to a patent
Prostamax	Lys-Glu-Asp-Pro (KEDP)	Prostatic regulator	Thin, and almost all of it chromatin biophysics
Crystagen	Glu-Asp-Pro (EDP)	Immunoprotector	One indexed study
Chonluten	Glu-Asp-Gly (EDG)	Bronchoprotector	One indexed cell-culture study; no rodent or human work

Two compounds in that table already have their own pages on this site and are not rewritten here: Epitalon, the AEDG tetrapeptide studied as a telomerase activator, and Pinealon, the EDR tripeptide. Both belong to this programme and both are worth reading alongside this page, because Epitalon is the family’s best-supported member and Pinealon is a clean example of how thin the tail gets. Other members exist that this site does not stock or describe — Livagen (KEDA), Testagen (KEDG), Thymogen (Glu-Trp, also known as oglufanide) and several dozen more in the 2022 table.

The proposed mechanism, and how much of it is demonstrated

The programme rests on one unifying claim: that ultrashort peptides reach the cell nucleus, interact with DNA and chromatin in a sequence-dependent manner, and thereby modulate gene expression. It is a strong claim — a two-to-four residue molecule acting as a specific transcriptional regulator is not how regulation is usually understood to work — and it deserves to be taken apart into the steps that have actually been tested.

Step one: do the peptides get in?

Fedoreyeva and colleagues (Biochemistry (Mosc), 2011, PMID 22117547) incubated HeLa cells with fluorescein-labelled Epitalon, Pinealon and Testagen and reported fluorescence in cytoplasm, nucleus and nucleolus. That establishes cellular and nuclear access for labelled peptide in that system. Separately, Khavinson et al. (Int J Mol Sci, 2022, PMID 35887081) argue that the family is carried by the proton-coupled oligopeptide transporters (PEPT1/PEPT2) and L-type amino-acid transporters — a plausible route, since those carriers are the known di- and tripeptide transport machinery, and the paper is a review and modelling exercise rather than a transport measurement for each named compound.

Step two: do they bind nucleic acid selectively?

The same 2011 study measured fluorescence quenching (Stern-Volmer constants) for peptide binding to labelled deoxyribooligonucleotides and reported that the constants differ by peptide sequence and by oligonucleotide sequence, including by cytosine methylation status, with Epitalon, Pinealon and Bronchogen binding preferentially to CNG-containing oligonucleotides. A companion study (Fedoreyeva et al., 2013, PMID 23581987) reported binding to labelled wheat histones H1, H2B, H3 and H4. These are real biophysical measurements and they are the strongest technical support the hypothesis has. They are also measurements of binding in solution, not of transcription in a cell.

Step three: does binding cause the gene-expression changes reported?

This is the step that is not closed. Gene-expression work exists — microarray analysis of mouse heart after Cortagen administration (PMID 15159690), qPCR panels in aging human mesenchymal stem cell cultures for KE, KED and AED (Ashapkin et al., Mol Biol Rep, 2020, PMID 32399807), and a large systematic review from the group collating these results (Khavinson et al., Molecules, 2021, PMID 34834147). What is absent is the connecting experiment: a demonstration that a specific measured peptide–DNA interaction is the cause of a specific measured transcriptional change, with the alternative explanations excluded. Until that exists, the mechanism is a coherent hypothesis with supporting biophysics, and it should be described that way.

A separate line: chromatin decondensation

A Tbilisi group (Lezhava, Monaselidze, Jokhadze and colleagues) has published repeatedly on a different endpoint — the physical condensation state of chromatin in cultured lymphocytes from donors aged roughly 75 to 88. Their reports describe deheterochromatinisation, increased sister-chromatid exchange frequency and reactivation of nucleolar organiser regions after exposure to Vilon, Epitalon, Livagen, Prostamax and Cortagen (PMID 15105581 in Biogerontology; PMID 15085253; PMID 33526740; PMID 37042594). It is worth noting plainly that increased sister-chromatid exchange is conventionally read as a marker of genomic instability, not as a favourable finding, and that these papers present it as evidence of chromatin activation. That interpretive choice is the group’s, and a reader should register it.

The state of the evidence base

Volume is not the weak point here. Depth, independence and design are.

Concentration in one group

A PubMed author search for V. Kh. Khavinson returns several hundred indexed records. Of the roughly fifty primary papers assembled for this page and the nine compound pages beneath it, almost every one lists Khavinson or a direct institutional collaborator among its authors. Two partial exceptions were identified and are named on the relevant pages: a Pavlov University pulmonology group in St Petersburg (Kuzubova, Titova and colleagues) publishing on Bronchogen in a rat model without Khavinson as an author, and the Tbilisi chromatin group above, which publishes on Prostamax without him on some papers while co-publishing with him on others. That is the extent of the independence found. A field in which a single laboratory network is the near-exclusive source of positive findings has not been tested in the way normal science tests things, however many papers it contains.

Venue and language

The bulk of the corpus sits in a small set of journals — Bulletin of Experimental Biology and Medicine, Advances in Gerontology (Uspekhi Gerontologii), Neuroendocrinology Letters, Georgian Medical News, Biofizika — and a substantial fraction is Russian-language with only an English abstract indexed. This is a real barrier rather than an excuse for either side of the argument: the work should not be dismissed for being Russian, and it also cannot be assessed by an English-language reader who can only see the abstract. Where this site could read only an abstract, it says so.

Code names and traceability

The group’s papers often designate compounds by internal laboratory codes — T-31, T-38, T-32, D-7, R-1, RR-1, AB-9, AB-17 — without giving the sequence in the same paper. A reader who wants to know which molecule was tested in a given experiment must sometimes find a second paper that maps the code. Cartalax is the clearest case: the AED tripeptide appears as “T-31” in some papers and as “Cartalax” or “AED” in others. This is not fraud, but it is a real obstacle to auditing the literature, and it means secondary summaries frequently attribute findings to the wrong compound.

Human data

Human reports exist. The group has published a review specifically collating them (Khavinson, Kuznik & Ryzhak, Adv Gerontol, 2013, PMID 24003726, Russian-language). The individual human studies located for the compounds on this site are small, open-label and without randomisation or blinding — for example the Vesugen and Pinealon report in 32 subjects with no control group (PMID 26390612) and the Pancragen report in 33 patients (PMID 22448364). Studies of that design cannot separate an effect of the compound from expectation, regression to the mean or observer bias, and no independently replicated randomised controlled trial of any compound in this family was found in indexed sources. Nothing on this site should be read as suggesting otherwise.

Negative and null findings do appear

To the literature’s credit, it is not uniformly positive. Cortagen produced no comitogenic effect on thymocyte proliferation where Vilon did (PMID 12420072), and did not affect immune or haemostatic parameters in hypophysectomised chickens where Epitalon did (PMID 19432169). Vesugen had no effect on the differentiation capacity of pineal immune cells (PMID 22803057). Crystagen did not affect cell renewal in ageing spleen (PMID 28976144). The presence of these nulls is a point in the corpus’s favour and is reported on the individual pages rather than filtered out.

How to read this literature critically

For a researcher evaluating whether to work with any of these compounds, the useful discipline is a short set of questions applied to every claim encountered:

Which molecule, exactly? An extract (thymalin, epithalamin, cortexin) is not the synthetic peptide named after it. A code name is not a sequence. Establish the sequence before accepting the finding.
Which model? Organotypic explant culture, dissociated cell culture, rodent, primate and human are four different evidentiary levels, and a great deal of this corpus sits at the first two. Effects reported at 10⁻¹² M in explant culture are a long way from anything else.
Who are the authors? Check the full author list, not the first three. The independence question is answered there.
Is it primary or is it the same table again? A large share of what circulates online is the 2022 review’s designation table restated. One table cited a hundred times is still one source.
What does the citation actually support? Several designations in that table — cardioprotector, chondroprotector, immunoprotector for Crystagen — are cited to patents rather than to studies. A patent documents a claim and a synthesis; it is not peer-reviewed evidence of activity.
Was the endpoint favourable, or interpreted as favourable? The sister-chromatid-exchange case above is the model for this question.

Applied honestly, that checklist leaves the family in a specific place: a real, internally consistent research programme with genuine biophysical measurements behind its central hypothesis, a large but narrow publication record, and no independently replicated demonstration of any of its assigned designations. That is neither a debunking nor an endorsement. It is what the record supports.

How to verify these compounds yourself

The scientific uncertainty above has nothing to do with the analytical questions, and the analytical questions are answerable. For peptides this small, two things carry the weight:

Mass spectrometry is unusually decisive here. These molecules differ from one another by one residue, and several family members are close in mass. Because they share the Glu-Asp core, a measured mass is often the only practical way to tell one from another — a certificate showing the expected mass for the specific sequence is what distinguishes Cartalax (AED, ~333 Da) from Pinealon (EDR, ~418 Da) or Cortagen (AEDP, ~430 Da).
HPLC purity is easier to achieve at this length than for a 30-residue peptide, since a dipeptide or tripeptide synthesis has far fewer opportunities to accumulate deletion sequences. A high purity figure on a tripeptide is therefore less informative than the same figure on a long peptide — which is exactly why the mass-spec identity line matters more.
Counter-ion and net peptide content are worth reading on any short, charged sequence, because a large fraction of the vial mass can be counter-ion and water rather than peptide. That is a documentation question, not a purity failure.

See how to read a COA for what each certificate line means, and how to verify peptide purity for how the analytical methods fit together. A specific batch can be checked on the self-serve verify tool.

Research-grade sourcing and verification

Most of this family is not held in stock. The compounds listed on our sourcing catalogue as available to order are ones our supplier lists and we have not bought; material of that kind typically takes about two to three weeks to reach us. For laboratory research use only, material is supplied with a per-batch Certificate of Analysis reporting HPLC purity (%) and mass-spec identity confirmation, verifiable at the lot level. Whatever one concludes about the biology, the identity and purity of the material in the vial are documented rather than assumed — and given how much of this family is chemically similar, that documentation is the part a researcher can rely on. This is sourcing and quality-assurance framing only.

Sourcing catalogue Epitalon 50 mg Pinealon 10 mg

Verify a batch

Every order ships with a per-batch Certificate of Analysis. Have a vial in hand? Enter its lot number to look up the COA for that exact batch.

Verify a batch →How to read a COA

Individual compound pages

Each page below is deliberately short. Where a compound supports only a few hundred words of honest content, that is what it gets — the alternative is padding, and padding in a family this thinly evidenced would be dishonest twice over.

Vilon (KE) — the dipeptide with the largest primary literature in the family, including rodent lifespan and carcinogenesis work.
Cortagen (AEDP) — derived from the cortexin extract; peripheral-nerve and gene-expression studies.
Vesugen (KED) — the tripeptide assigned to vascular tissue; cell-culture and molecular-docking work.
Pancragen (KEDW) — the only family member with a non-human primate study.
Bronchogen (AEDL) — the clearest Khavinson-free rodent work, and a sequence discrepancy in its own literature.
Cartalax (AED) — designated a chondroprotector, studied in skin, kidney and stem cells.
Cardiogen (AEDR) — two rodent studies; the cardiac designation traces to a patent.
Prostamax (KEDP) — almost entirely chromatin calorimetry rather than prostate work.
Crystagen (EDP) — one indexed study; the thinnest page on this site, honestly.
Chonluten (EDG) — one indexed cell-culture study, and why it is not the same molecule as Bronchogen.
Epitalon (AEDG) and Pinealon (EDR) — existing pages, unchanged.

Frequently asked questions

What are peptide bioregulators?

It is the collective name for a family of very short synthetic peptides — mostly two to four amino acids — developed from the 1970s onward by V. Kh. Khavinson and colleagues at the St Petersburg Institute of Bioregulation and Gerontology. Each carries a trade name (Vilon, Cortagen, Vesugen, Pancragen and so on) and a nominal target tissue. They are research chemicals here, described as molecules and as a literature, with no use, effect or benefit claimed.

Is the peptide bioregulator mechanism established?

No. The proposed mechanism — that ultrashort peptides enter the nucleus, bind DNA in a sequence-selective way and modulate transcription — is a hypothesis advanced and developed by the originating group. Biophysical binding studies do exist and are cited on this page, but the chain from a measured binding constant to a specific gene-expression change in an intact organism is not independently established.

How much of this literature is independent of the originating group?

Very little. A PubMed author search returns several hundred indexed records for V. Kh. Khavinson, and the overwhelming majority of papers on the named compounds list him or a direct collaborator as an author. The nearest things to independent work identified for this page are a Pavlov University pulmonology group in St Petersburg publishing on Bronchogen, and a Tbilisi State University chromatin-biophysics group publishing on Prostamax and Vilon — and even the latter co-publishes with Khavinson elsewhere.

Are there human clinical trials of the peptide bioregulators?

There are human reports in the indexed literature, but the ones this page could verify are small, open-label, non-randomised and non-blinded, and originate from the same institutional network. No independently replicated randomised controlled trial of any compound in this family was located in indexed sources.

Why do the same peptides appear under code names like T-31, T-38, D-7 and AB-9?

The group's own papers frequently use internal laboratory codes rather than trade names or sequences, and the mapping is not always given in the paper that uses the code. That practice makes it genuinely difficult for an outside reader to trace which molecule was tested in which experiment, and it is one reason this literature is harder to audit than its volume suggests.

Which compounds are in this family?

The most commonly encountered are Vilon (KE), Epitalon (AEDG), Pinealon (EDR), Cortagen (AEDP), Vesugen (KED), Cartalax (AED), Crystagen (EDP), Bronchogen (AEDL), Cardiogen (AEDR), Pancragen (KEDW) and Prostamax (KEDP). A 2022 review from the originating group tabulates several dozen more.

Literature cited

Khavinson V, Linkova N, Kozhevnikova E, Dyatlova A, Petukhov M, Ruvo M, Doti N. “Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers.” Int J Mol Sci. 2022;23(14):7733. PMID 35887081. pubmed.ncbi.nlm.nih.gov/35887081 (source of the family sequence/designation table; review from the originating group).
Khavinson VK, Popovich IG, Linkova NS, Mironova ES, Ilina AR. “Peptide Regulation of Gene Expression: A Systematic Review.” Molecules. 2021;26(22):7053. PMID 34834147. pubmed.ncbi.nlm.nih.gov/34834147.
Fedoreyeva LI, Kireev II, Khavinson VKh, Vanyushin BF. “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;76(11):1210–1219. PMID 22117547. pubmed.ncbi.nlm.nih.gov/22117547.
Fedoreyeva LI, Smirnova TA, Kolomijtseva GY, Khavinson VKh, Vanyushin BF. “Interaction of short peptides with FITC-labeled wheat histones and their complexes with deoxyribooligonucleotides.” Biochemistry (Mosc). 2013;78(2):166–175. PMID 23581987. pubmed.ncbi.nlm.nih.gov/23581987.
Anisimov SV, Khavinson VKh, Anisimov VN. “Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarray.” Neuro Endocrinol Lett. 2004;25(1–2):87–93. PMID 15159690. pubmed.ncbi.nlm.nih.gov/15159690 (source of the “directed synthesis from Cortexin” description).
Khavinson VKh, Lezhava TA, Malinin VV, et al. “Effects of short peptides on lymphocyte chromatin in senile subjects.” Bull Exp Biol Med. 2004;137(1):78–81. PMID 15085253. pubmed.ncbi.nlm.nih.gov/15085253.
Lezhava T, Khavison V, Monaselidze J, et al. “Bioregulator Vilon-induced reactivation of chromatin in cultured lymphocytes from old people.” Biogerontology. 2004;5(2):73–79. PMID 15105581. pubmed.ncbi.nlm.nih.gov/15105581.
Lezhava T, Jokhadze T, Monaselidze J, et al. “Epigenetic modification under the influence of peptide bioregulators on ‘aged’ heterochromatin.” Georgian Med News. 2020;(309):120–124. PMID 33526740. pubmed.ncbi.nlm.nih.gov/33526740.
Khavinson VK, Anisimov VN, Zavarzina NY, et al. “Effect of vilon on biological age and lifespan in mice.” Bull Exp Biol Med. 2000;130(7):687–690. PMID 11140587. pubmed.ncbi.nlm.nih.gov/11140587.
Khavinson VKh, Rybakina EG, Malinin VV, et al. “Effects of short peptides on thymocyte blast transformation and signal transduction along the sphingomyelin pathway.” Bull Exp Biol Med. 2002;133(5):497–499. PMID 12420072. pubmed.ncbi.nlm.nih.gov/12420072 (reports a null result for Cortagen).
Ashapkin V, Khavinson V, Shilovsky G, Linkova N, Vanyushin B. “Gene expression in human mesenchymal stem cell aging cultures: modulation by short peptides.” Mol Biol Rep. 2020;47(6):4323–4329. PMID 32399807. pubmed.ncbi.nlm.nih.gov/32399807.
Kraskovskaya N, Linkova N, Sakhenberg E, et al. “Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes.” Int J Mol Sci. 2024;25(21):11363. PMID 39518916. pubmed.ncbi.nlm.nih.gov/39518916.
Khavinson VKh, Kuznik BI, Ryzhak GA. “Peptide bioregulators: the new class of geroprotectors. Message 2. Clinical studies results.” Adv Gerontol. 2013;26(1):20–37. PMID 24003726. pubmed.ncbi.nlm.nih.gov/24003726 (Russian-language; English abstract only was available for this page).
Meshchaninov VN, Tkachenko EL, Zharkov SV. “Effect of synthetic peptides on aging of patients with chronic polymorbidity and organic brain syndrome of the central nervous system in remission.” Adv Gerontol. 2015;28(1):62–67. PMID 26390612. pubmed.ncbi.nlm.nih.gov/26390612 (32 subjects, uncontrolled).

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