Preloaded Autoinjector | Livagen | 3ml Pen | 20mg

The Livagen pen is a preloaded 3ml research autoinjector holding 20mg of the synthetic tetrapeptide H-Lys-Glu-Asp-Ala-OH in solution, putting the concentration at 20/3 mg/ml. Adding an alanine to the KED sequence creates an internal Asp-Ala bond, and that single bond turns aspartyl chemistry into the most likely covalent degradation route, one whose main product weighs exactly what the parent weighs.

Specification Table

What Changes When Livagen Ships in Solution?

Water switches on two backbone reactions in this tetrapeptide, and the more likely of the two produces a degradation product that weighs the same as the intact molecule, which is an awkward property for anyone verifying a lot by mass.

The absences come first, because they remove most of the usual worry list. There is no asparagine or glutamine, so classical deamidation cannot occur. There is no methionine, cysteine, tryptophan, tyrosine or histidine, so oxidation has no target and there is no disulfide to scramble. There is no aromatic ring anywhere, so no near-UV chromophore exists and light protection is generic prudence rather than a mechanism. Aggregation is equally absent: a small, charge-rich tetrapeptide, net negative at neutral pH, neither self-associates nor binds hard to anionic borosilicate glass.

What the added alanine changes is the aspartate. In the shorter KED sequence the aspartate sits at the C-terminus with nothing following it, which limits classical aspartimide chemistry because that reaction needs a following backbone nitrogen to cyclise onto. Append an alanine and the aspartate acquires exactly that. Asp3-Ala4 is a context that supports succinimide formation: the aspartate side chain closes onto the next amide nitrogen, water leaves, and a five-membered succinimide ring forms. Hydrolysis of that ring reopens it to a mixture of ordinary aspartate and isoaspartate, and the isoaspartate form has the same molecular formula and the same 461.5 g/mol as the compound that went in. It is an isomer rather than a fragment, and intact-mass measurement cannot tell them apart.

The same Asp-Ala bond is also the one most exposed to acid-catalysed cleavage, which would split the tetrapeptide into a tripeptide and free alanine. That route does change mass and is detectable.

The second live reaction is inherited from the N-terminal pair. Lys-Glu is the whole of the dipeptide sold as Vilon, and a free N-terminal amine on a Lys-Glu unit cyclises to its diketopiperazine in aqueous solution. In a tetrapeptide the ring closure becomes a clipping reaction: cyclo(Lys-Glu) leaves at roughly 257.3 g/mol and the Asp-Ala dipeptide remains at about 204.2, and the two sum to 461.5, since the water lost in forming the ring is regained in cleaving the amide bond. Those two new peaks are unmistakable on any instrument.

So a standing fill can degrade by one route that shows up immediately and one that hides behind an identical mass. Neither has been characterised experimentally for this compound, so both are inference from general peptide chemistry rather than published measurement. No Western-approved product exists, which means no manufacturer has had to publish a buffer and pH answer to any of it.

What Is Known About Livagen Solution Stability?

No compound-specific aqueous stability study and no preloaded-solution formulation study was located, so Livagen solution stability is inferred from the structure rather than measured over a shelf life.

The inference has a direction. Succinimide formation at Asp3-Ala4 is base-catalysed and accelerates above neutral pH; Asp-Xaa cleavage is acid-catalysed; the N-terminal ring closure accelerates with heat and with neutral to basic pH. Temperature pushes all three the same way, which is why refrigeration is the intervention that matters, while pH pushes them in opposite directions, so no single formulation pH suppresses everything.

What makes Livagen solution stability harder to audit than it looks is the isomer. A certificate reporting correct intact mass and a clean chromatogram at release says nothing about the isoaspartate fraction six weeks later, because that species carries the parent mass and elutes close to the parent on an ordinary reversed-phase method. The measurement that answers the question is a separation developed against an authentic isoaspartate standard, or a methyltransferase-based assay, and neither is a routine release test.

What Does the Livagen Pen Deliver Per Increment?

Concentration is 20 mg divided by 3 ml, and every figure below follows from that division and a molecular weight of 461.5 g/mol.

Molar concentration is (20/3 divided by 461.5) multiplied by 1000, which reduces to 20 × 0.722 mM. Mass delivered per 0.01 ml, the smallest increment most pen mechanisms resolve, is (20/3) × 0.01 mg; per 0.1 ml it is (20/3) × 0.1 mg. At a 10 mg fill the figures become concrete: 3.333 mg/ml, 7.22 mM, 33.3 micrograms per 0.01 ml, 333 micrograms per 0.1 ml.

Low molecular weight raises the molar figure relative to what people carry over from larger peptides. The same 10 mg of a 1300 g/mol decapeptide gives about 2.6 mM; this tetrapeptide gives 7.22 mM, roughly 2.8 times as many moles for identical mass. That correction matters whenever an experiment is designed in moles and the material is purchased in milligrams.

Against the published work the arithmetic has nothing to anchor to. Developer-group in vitro studies use low concentrations, commonly nanomolar to micromolar in culture, so reaching 1 micromolar from a 7.22 mM fill is about a 7,200-fold dilution. No human dose has been established in any controlled study, so there is no research figure a device increment can be compared with, and any listing implying otherwise is unverified.

Does Livagen Come in a Pen, and How Does It Compare With a Vial?

Yes: this product is that device, and the Livagen pen vs vial comparison comes down to one variable, which is how long the tetrapeptide has been dissolved before it is drawn.

Anyone asking does Livagen come in a pen is usually measuring it against the norm in the source literature, where peptides of this class are supplied as lyophilized powder and reconstituted immediately before use. Freshly prepared solution is what the developer-group experiments used, and a cartridge held for weeks is a presentation that literature never tested.

What the format removes is set out on the pen versus vial comparison and across the preloaded autoinjector range. Against a lyophilized vial presentation, which keeps the material dry until the day of use and lets the cake be inspected first, the Livagen pen vs vial trade is preparation variance against time in water.

Over days that trade favours the cartridge, since preparation variance dominates and the backbone reactions have had little time. Over months it favours the vial, and more so here than for a compound whose degradation is easy to detect, because the isoaspartate route accumulates without announcing itself. A nasal presentation of the same compound carries identical aqueous chemistry in a different container.

Livagen Pen Storage in Practice

Refrigerate at 2-8°C, do not freeze, and keep time at ambient temperature to a minimum, because all three candidate degradation routes are thermally accelerated and temperature is the only variable a laboratory actually controls.

Storage here is simpler than for most compounds in this catalogue, for an unusual reason: there is nothing to protect from light in a chemical sense. No aromatic residue means no chromophore in the near-UV or visible range, so bench illumination drives no photochemistry.

Freezing risks the cartridge and gains nothing, since this molecule has no aggregation liability a frozen state would suppress. Good practice means recording the date of first actuation and the interval before each subsequent draw, because for a device in service across weeks that interval is an experimental variable. The lever that cannot be pulled is formulation pH, which is not disclosed, and since the routes respond to pH in opposite directions, that omission removes any way of predicting which one dominates.

What the Product Record Does Not State

Four fields are missing, and one of them is missing in a way that is unusual even for a research-format product: this compound has no trustworthy registry number.

The CAS number is unverified. No reliable registry entry was located, and the value circulating on vendor and broker listings is inconsistent with a tetrapeptide of this formula, so it should not be relied on for ordering or for regulatory paperwork. Confirm identity against the sequence and the formula rather than against a number.

Solution pH is unpublished, and it decides which of the degradation routes dominates, since succinimide formation is base-catalysed while Asp-Xaa cleavage is acid-catalysed. Without it, no degradant estimate is possible even in principle.

The excipient system is unpublished, and whatever buffer sets that pH also enters any assay the solution is added to. The counter-ion and net peptide content are unpublished too. Acetate is the usual research salt, and for a molecule of 461.5 g/mol the counter-ion is a larger fraction of total mass than it would be for a large peptide, so a gravimetric fill at nominal 20 mg contains less peptide than the label suggests. Fill date and shelf-life data are absent as well. Request all of it against the certificate of analysis, alongside the checks in peptide storage and stability.

Verifying a Livagen Pen and Confirming Its Contents

Verification here has to answer two different questions, because one degradation route changes mass and the other does not, and a single measurement will not cover both.

Inspect the solution against a white background before each draw: clear, colourless, no particulate. Then accept that the inspection has told you little, since the parent, its isomer and both fragments are colourless and freely soluble.

Mass spectrometry answers the clipping question well. Intact mass against 461.5 g/mol average or 461.21 Da monoisotopic confirms the parent; N-terminal clipping produces peaks near 257.3 and 204.2, and Asp-Ala cleavage produces a tripeptide plus free alanine. Those are visible shifts and the ratio of parent to fragment gives a direct read on how far the fill has travelled.

Mass spectrometry does not answer the isoaspartate question at all, because that species carries the same formula and the same mass. Separating it needs a chromatographic method developed against an authentic isoaspartate standard, or a protein isoaspartyl methyltransferase assay, run against a freshly prepared reference on the same day. Neither is a routine release test, which is why a clean certificate at release cannot settle the question for a device that has been in service for two months.

Quantitation cannot use absorbance at 280 nanometres, since none of these species contains tryptophan or tyrosine. Use the peptide bond at 205 to 214 nanometres, a colourimetric assay, or amino acid analysis, which also reports the residue ratio and so catches clipping directly. Bring the cartridge to room temperature before actuating: viscosity falls as it warms, and a spring-driven mechanism meters a thinner solution differently.

What the Literature Reports and Where It Comes From

The published record is small, largely from one research lineage, and centres on chromatin rather than on the organ the trade name points at, which is worth knowing before reading any single result.

In indexed journals the molecule appears as KEDA rather than under its trade name. It was developed by V. Kh. Khavinson and colleagues at the St Petersburg Institute of Bioregulation and Gerontology, and the association with liver tissue is real in the developer literature: Kuznik and colleagues examined a polypeptide liver complex alongside the tetrapeptide KEDA in 2020, which is the concrete basis for the name.

The best-documented experimental effect, though, is on chromatin. Khavinson, Lezhava and Malinin reported in 2004 that short peptides of this class altered lymphocyte chromatin in elderly donors, and Lezhava and Jokhadze reported in 2007 on activation of pericentromeric and telomeric heterochromatin in cultured lymphocytes from old individuals. Khavinson and colleagues reported in 2002 on tissue-specific action of peptides in rat tissue culture across ages. These are small, mostly single-group studies, several on the class rather than this compound alone, with little independent replication.

The proposed mechanism is not a classical receptor interaction. The developer-group hypothesis, set out in a 2021 systematic review in Molecules, is that short peptides enter cells, reach the nucleus, bind DNA sequence-selectively and modulate gene expression, including reported decondensation of heterochromatin in aged cells. Read that as a hypothesis from one lineage rather than as established pharmacology. Wider context sits in the bioregulator research overview, and a related tetrapeptide of the same family is listed as Ovagen.

What has not been studied should be stated as plainly as what has. There is no controlled human trial of the injected route for any endpoint, no independent replication of the liver or chromatin claims, no pharmacokinetic data, and no solution-stability data for a device. Rapid peptidase clearance would be expected of a tetrapeptide, but that is inference rather than measurement.

Safety and Regulatory Position

Few adverse effects appear in the published studies, and those studies are small and not powered to detect harm, so the absence of reported findings is not evidence of safety.

This compound is not approved as a drug by the FDA, EMA, PMDA, TGA or Health Canada. It was developed and patented in Russia, and while some peptides from that group are registered as medicines or sold as parapharmaceuticals within the Russian Federation, the precise Russian status of this tetrapeptide is unverified here. In Western markets it is a research chemical.

No FDA-approved labelling exists, so there is no reference specification against which a supplier certificate can be compared, and the absent CAS number removes another identifier that paperwork usually relies on. Presence on the FDA 503A or 503B bulk drug substance lists for pharmacy compounding was not confirmed in the sources used here and is unverified. No entry for it was found on the WADA Prohibited List, and the current list was not checked directly, so treat that as unconfirmed. Safety of chronic self-administration is unstudied.

What Does the Chromatin Work on Livagen Actually Report?

The most cited result for this tetrapeptide concerns chromatin structure in human lymphocytes. Khavinson’s group reported that adding the peptide to cultured cells from older donors loosened densely packed regions of the nucleus, a change they described as deheterochromatinization, and that ribosomal genes previously silent in those cells became transcriptionally active again. The measurement was made by cytological staining and by counting nucleolar organiser regions rather than by sequencing.

Chromatin decondensation is the general term for what was claimed. Densely wound chromatin condensation keeps genes physically inaccessible to the transcription machinery, so a compound that loosens the packing would in principle restore protein synthesis from genes that had been shut away. The reported effect was larger in cells from donors over sixty than in cells from young donors, which is the observation the age-reversal framing is built on.

What the work does not establish is the step in between. No study has shown the intact peptide entering a human cell nucleus, and the binding model, in which short peptides recognise specific DNA sequences in promoter regions, comes from modelling and from gel-shift assays rather than from structures. Chromatin decondensation has also never been reported for this peptide in a living animal, only in culture. Anyone citing the result should cite it as a cell-culture finding from one laboratory.

Why Is Livagen Described as a Liver Bioregulator?

Because of where the parent extract came from, not because of anything in the sequence. The Livagen peptide was designed as a defined replacement for a liver tissue extract in Khavinson’s organ-by-organ programme, so liver function became its assigned indication before any liver experiment was run on the synthetic version. KEDA has no known liver-specific transporter, receptor or enzyme target.

The experimental record on liver function is correspondingly thin. Rodent studies from the same group report improved biochemical markers after toxic insult, which is where the detoxification language originates, but the models are acute and the endpoints are serum enzymes rather than histology. Work on the gastrointestinal tract is thinner still. Reports of activity against enkephalin-degrading enzymes appear in review articles more often than in primary papers, and the primary source for that claim is difficult to trace.

Naming conventions add to the confusion. Peptide bioregulators in this family are named for their assigned organ, so the name itself asserts a tissue specificity that the evidence does not carry. Livagen is a tetrapeptide bioregulator by design and a liver agent by nomenclature. Those are two different claims and only the first one is settled.

How Is Livagen Grouped With Other Research Peptides?

Supplier catalogues and clinic lists place this compound in two overlapping groups, and the grouping logic differs between them. The first group is the Khavinson family itself: Vilon, Epitalon, Bronchogen and the rest, all short peptide bioregulator sequences from the same St. Petersburg programme run by Vladimir Khavinson, all sharing a claim structure about gene expression and all carrying comparable, modest evidence. Within that group the Livagen peptide is neither the best nor the worst supported.

The second group is looser and less defensible. Lists of research peptides routinely put the Livagen peptide next to BPC-157 and MOTS-c, which have nothing in common with it. BPC-157 is a fifteen-residue gastric fragment with a substantial rodent literature on tendon and gut injury. MOTS-c is a sixteen-residue peptide encoded in mitochondrial DNA and studied for metabolic effects. Neither is a Khavinson bioregulator, neither acts on chromatin, and grouping all three under one heading tells you about catalogue structure rather than pharmacology. Claims about circadian rhythm belong to Epitalon in this family, not to this molecule.

Peptide therapy providers compound the problem by listing the whole set as interchangeable options. They are not interchangeable. Each has its own evidence base, its own stability behaviour and its own regulatory position, and this pen is supplied for laboratory research rather than as any kind of treatment. A lot-specific CoA is the only document that tells you which molecule is actually in front of you, whichever list the name was taken from.

Published Literature

Five entries, each confirmed against a primary index before listing here. All concern the compound or its short-peptide class; the device format has no published record.

1. Khavinson VKh, Malinin VV, Chalisova NI, et al. Tissue-specific action of peptides in tissue culture of rats of various ages. Adv Gerontol. 2002;9:95-100. PMID: 12096446
2. Khavinson VKh, Lezhava T, Malinin VV. Effects of short peptides on lymphocyte chromatin in senile subjects. Bull Exp Biol Med. 2004;137(1):78-81. DOI: 10.1023/B:BEBM.0000024393.40560.05 PMID: 15085253
3. Lezhava T, Jokhadze T. Activation of pericentromeric and telomeric heterochromatin in cultured lymphocytes from old individuals. Ann N Y Acad Sci. 2007;1100(1):387-399. DOI: 10.1196/annals.1395.043 PMID: 17460203
4. Kuznik BI, Khasanova NB, Ryzhak GA, et al. The influence of polypeptide liver complex and tetrapeptide KEDA on organism physiological function in norm and age-related pathology. Adv Gerontol. 2020;33(1):159-164. PMID: 32362099
5. Khavinson VKh, Popovich IG, Linkova NS, et al. Peptide regulation of gene expression: a systematic review. Molecules. 2021;26(22):7053. DOI: 10.3390/molecules26227053 PMID: 34834147

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