Livagen Research, Specifications & Scientific Information

Introduction

Livagen is the hepatic member of the Khavinson bioregulator series — Lys-Glu-Asp-Ala, four residues, 461 daltons — and it is the one member with a number attached to a mechanism.

That number is an inhibition constant. In human serum the tetrapeptide inhibited enkephalin-degrading enzymes with a half-maximal inhibitory concentration of 20 micromolar, against 500 micromolar for Epitalon measured in the same assay, and it did so more efficiently than puromycin, leupeptin and D-PAM. The same paper ran a radioreceptor assay against mu- and delta-opioid receptors in rat brain membranes and reported no interaction at all ^[6]. A measured potency and a published negative control are both unusual in this literature, and together they are the most concrete biochemical statement anywhere in this batch.

The rest of the compound's record sits inside the family's ordinary limitations, which are stated once here. The primary work comes from the St Petersburg Institute of Bioregulation and Gerontology, a cytogenetics group in Tbilisi and Russian Academy of Sciences collaborators; several papers are published only in Russian; group sizes are small or unstated; the emphasis is on cultured cells and organotypic explants; and none of the central findings has been independently replicated. No clinical study of this tetrapeptide has been identified at all.

What Is Livagen?

A synthetic tetrapeptide with free termini, KEDA in single-letter code: L-lysyl-L-alpha-glutamyl-L-alpha-aspartyl-L-alanine. Russian-language papers transliterate the name Lyvagen as well as Livagen.

It was obtained, in the words of the paper that used it first in hepatocyte culture, by directed chemical synthesis on the basis of amino acid analysis of liver polypeptide preparations ^[5]. That sentence is the series' design premise in compressed form: analyse the amino acid composition of a tissue extract, synthesise a short sequence from it, and test the sequence against the tissue it came from.

A 2001 experiment states the premise in its cleanest testable form. Explants from rat brain cortex, subcortical structures, liver and thymus were grown in organotypic culture and exposed to four peptides of the series — Cortagen, Epitalon, this tetrapeptide and Vilon. Each peptide was reported to stimulate growth of the explant from the tissue whose extract it had been designed from ^[7]. Four peptides, four tissues, four matches. It is the kind of result that is either a real demonstration of specificity or a pattern that a small unblinded experiment can produce on its own, and nothing published since has settled which.

Livagen has not been approved by the U.S. Food and Drug Administration for any indication. No marketing application is on record in the United States, and no study of it appears on ClinicalTrials.gov.

Livagen Specifications

PubChem carries the free tetrapeptide as compound identifier 87919683 with CAS registry number 433257-50-2, formula C18H31N5O9 and an average mass of 461.47 g/mol. No unique ingredient identifier resolves in the FDA/NCATS Global Substance Registration System, so that field is published as unknown rather than estimated. The sequence is written Lys-Glu-Asp-Ala in the primary literature and is transliterated Lyvagen in at least one Russian-language paper. One property of this tetrapeptide has actually been measured rather than assumed: peptide hydrolases of the rat small intestine were reported not to hydrolyse it to any appreciable extent, which makes it one of the very few compounds in this series with a published stability observation of any kind. Reagent material supplied as a salt will not match the free-peptide mass above.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does Livagen Work?

Not established — but for once the honest answer has a measured component, and it is worth separating that component from the rest.

What has been measured. Enkephalin-degrading enzyme activity in human serum was assayed by the rate of tritiated Leu-enkephalin hydrolysis. The tetrapeptide inhibited it with an IC50 of 20 µM. A concentration–inhibition curve was plotted. The comparator tetrapeptide from the same series gave an IC50 of 500 µM. Both were more efficient than three established peptidase inhibitors tested in the same system ^[6].

What was ruled out. The obvious downstream question — whether an effect on the endogenous opioid system runs through the receptors rather than the peptidases — was tested directly, using tritiated [D-Ala2, D-Leu5]-enkephalin in a radioreceptor assay against the rat brain membrane fraction. No interaction with mu- or delta-opioid receptors was observed ^[6]. Reporting that is an act of discipline; a negative result that narrows a claim is more useful than a positive one that widens it.

What does not follow. Serum peptidase inhibition at 20 micromolar does not explain the chromatin observations described below, which were obtained at nanogram-per-millilitre concentrations — several orders of magnitude lower. The two accounts of what this molecule does sit side by side in the literature with nothing published connecting them, and a compound with two disconnected mechanisms has, in evidentiary terms, none.

No receptor is proposed for the cell-culture effects, and the specification table therefore shows primary target, receptor family and agonist status as not publicly characterised.

One stability measurement exists. Peptide hydrolases of the rat small intestine were reported not to hydrolyse this tetrapeptide to any appreciable extent ^[4]. That is the closest thing in the batch to a published stability datum, and it is a statement about an enzyme preparation rather than a bioavailability figure. No pharmacokinetic dataset exists.

Livagen Mechanism of Action

In vitro research

Chromatin in lymphocytes from elderly donors. Lymphocytes cultured from old people were exposed to the tetrapeptide, and the reported effects were activation of ribosomal genes, decondensation of pericentromeric structural heterochromatin, and release of genes repressed through age-related condensation of euchromatic regions ^[1].

The pericentromeric result is the one to notice, because it distinguishes this compound from a sibling. In a comparison across five peptides in donors aged 75 to 88, all five activated ribosomal genes and decondensed facultative chromatin, but only some also decondensed pericentromeric structural heterochromatin of chromosome 1 — and this tetrapeptide and Epitalon were among those that also acted on chromosome 9, where Vilon did not act on the structural compartment at all ^[2]. Differences of that kind are what a series of related compounds ought to show if the sequences matter.

Chromosomal damage from a metal ion. In lymphocytes from donors aged 80 to 91 exposed to cobalt chloride, chromosomal aberrations rose significantly relative to a young control group. The tetrapeptide reduced the number of cobalt-induced changes to 3.4 ± 0.6% against 4.2 ± 0.7%, and shifted where sister chromatid exchanges occurred — cobalt alone concentrated them in pericentromeric heterochromatin, while cobalt with the peptide concentrated them in telomeric heterochromatin ^[3]. The reduction in aberrations is small and its error bars overlap; the redistribution of exchanges is the more distinctive observation and the paper presents it as the novel one.

Protein synthesis in hepatocytes. Monolayer cultures of hepatocytes from rats aged 1 to 24 months show a circumhoralian — roughly hourly — rhythm of protein synthesis. The tetrapeptide raised the level of protein synthesis at every age, most in cells from old animals, and in old rats increased the amplitude of the oscillation. Epitalon, tested in the same system, did not change the intensity of protein synthesis at all ^[5]. An effect on the amplitude of an oscillation rather than on its mean is a specific claim and an unusual one.

Organotypic liver explants. Explant growth from liver was stimulated where explants from three other tissues responded to their own matched peptides ^[7].

Everything in this section was observed in cultured cells, excised tissue or serum. None of it establishes anything about an intact animal, and none of it about a person.

Preclinical Research on Livagen

Animal research

Digestive enzymes in rats of different ages

Two weeks of oral administration to rats produced opposite effects by age: digestive enzyme activity fell in young animals and rose in old ones, with the activity in old rats after administration approaching, in most cases, the level seen in young control animals ^[4].

The same paper reports two other things worth keeping. The tetrapeptide was weakly hydrolysed, with intestinal peptide hydrolases not degrading it appreciably. And in vitro it reduced glycyl-L-leucine dipeptidase activity in the small intestine by 50% — another enzyme-inhibition result, in a different enzyme class from the serum work, at an unstated concentration.

An age-reversed direction of effect is the single most characteristic claim of this whole research programme, and it is also the hardest to interpret. A compound that moves a measurement towards the young value from either side is either normalising something or is being reported against a moving reference. Distinguishing those requires a pre-specified endpoint and a control group, and the indexed abstract describes neither.

Findings in this section were obtained in rats. Nothing in them establishes anything about humans.

What Is Livagen Being Researched For?

• Chromatin state in cells from elderly donors — ribosomal gene activity and heterochromatin decondensation ^{[1, 2]}.
• Protection against metal-ion-induced chromosome damage — cobalt chloride in lymphocytes from very old donors ^[3].
• Hepatocyte protein synthesis and its ultradian rhythm — amplitude and level across rat ages ^[5].
• Peptidase inhibition — enkephalin-degrading enzymes in human serum, and a dipeptidase in the small intestine ^{[6, 4]}.
• Digestive enzyme activity in ageing — oral administration in young and old rats ^[4].

None of that is research into, or evidence about, research-grade material supplied for laboratory use.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Livagen vs Related Compounds

Epitalon :: Ala-Glu-Asp-Gly, and the most informative comparator this compound has, because the two were tested head to head twice and separated both times. In hepatocyte culture this tetrapeptide raised protein synthesis and Epitalon did not ^[5]; in serum this one inhibited enkephalin-degrading enzymes twenty-five times more potently ^[6]. Two sequences from one programme that behave differently in shared assays are better evidence that sequence matters than any number of experiments in which they behave the same. Pancragen :: Lys-Glu-Asp-Trp, the nearest structural neighbour — the same three N-terminal residues, with tryptophan where this one carries alanine — and positioned against pancreas rather than liver. The claim that one terminal residue redirects the compound to a different organ is the series' premise at its strongest, and no scrambled-sequence or single-substitution control has been located that tests it. Vilon and Cortagen :: Tested beside this one in the four-peptide, four-tissue organotypic experiment and in the five-peptide chromatin comparison ^{[7, 2]}. Prostamax :: Lys-Glu-Asp-Pro, the fourth member of the KED-plus-one group, and tested alongside this one in the chromatin work in senile subjects ^[2].

Evidentiary position

Not approved by the U.S. Food and Drug Administration, no registered trial, no identified clinical study of any design, and a measured enzyme-inhibition result that has never been connected to the cellular observations.

No comparison of effect between these compounds is made on this page.

Chemical & Molecular Characteristics

Alanine at the C-terminus is the whole of what distinguishes this from its siblings. The Lys-Glu-Asp core is shared with Vesugen (which stops there), Pancragen (tryptophan), Testagen (glycine) and Prostamax (proline). Alanine contributes a methyl group and nothing else — no charge, no hydrogen-bond donor or acceptor beyond the backbone, and no appreciable volume. Any account of why this tetrapeptide is hepatic and its siblings are not has to carry that methyl group, and no published work has tested it directly.

Charge and polarity are severe. One lysine amine against the glutamate side chain, the aspartate side chain and the C-terminal carboxyl: net negative at physiological pH, highly water-soluble, and with essentially no hydrophobic surface. Reversed-phase retention on conventional C18 columns is correspondingly poor, and a peptide that elutes near the void volume is difficult to separate from salts and from synthesis-related impurities. What "purity by HPLC" means here depends almost entirely on the method.

No aromatic residue, so no absorbance at 280 nm. Quantification has to use peptide-bond absorbance near 214 nm, where solvents and buffers also absorb. This is one of the sharpest practical differences between this tetrapeptide and Pancragen, whose tryptophan makes quantification straightforward.

Aspartate and glutamate bring isomers of identical mass. Both residues undergo alpha/beta and alpha/gamma rearrangement under thermal and acidic stress, producing species with the same molecular formula and the same mass as the intended compound. Mass spectrometry confirms composition. It does not confirm that four residues are joined in the intended order through the intended bonds, and a sequencing method is what closes that gap.

One register field is empty. CAS registry number 433257-50-2 and PubChem compound identifier 87919683 both resolve; no FDA/NCATS unique ingredient identifier does. That field is shown as unknown above rather than filled from a neighbouring substance.

Frequently Asked Questions

Scientific References

1. Khavinson VKh, Lezhava TA, Monaselidze JG, et al.. Effects of Livagen peptide on chromatin activation in lymphocytes from old people Bulletin of experimental biology and medicine; 2002. PMID 12533768 doi:10.1023/a:1021924702103
2. Khavinson VKh, Lezhava TA, Malinin VV. Effects of short peptides on lymphocyte chromatin in senile subjects Bulletin of experimental biology and medicine; 2004. PMID 15085253 doi:10.1023/b:bebm.0000024393.40560.05
3. Lezhava T, Jokhadze T. Activation of pericentromeric and telomeric heterochromatin in cultured lymphocytes from old individuals Annals of the New York Academy of Sciences; 2007. PMID 17460203 doi:10.1196/annals.1395.043
4. Timofeeva NM, Khavinson VKh, Malinin VV, et al.. [Effect of peptide Livagen on activity of digestive enzymes in gastrointestinal tract and non-digestive organs in rats of different ages] Advances in gerontology = Uspekhi gerontologii; 2005. PMID 16075683
5. Brodskiĭ VIa, Khavinson VKh, Zolotarev IuA, et al.. [Rhythm of protein synthesis in cultures of hepatocytes from rats of different ages. Norm and effect of the peptide livagen] Izvestiia Akademii nauk. Seriia biologicheskaia; 2001. PMID 15926314
6. Kost NV, Sokolov OIu, Gabaeva MV, et al.. [Effect of new peptide bioregulators livagen and epitalon on enkephalin-degrading enzymes in human serum] Izvestiia Akademii nauk. Seriia biologicheskaia; 2003. PMID 12942748
7. Khavinson VK. Tissue-specific effects of peptides Bulletin of experimental biology and medicine; 2001. PMID 11713572 doi:10.1023/a:1013058701974
8. Khavinson VK, Popovich IG, Linkova NS, et al.. Peptide Regulation of Gene Expression: A Systematic Review Molecules (Basel, Switzerland); 2021. PMID 34834147 doi:10.3390/molecules26227053

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.