Pancragen Research, Specifications & Scientific Information

Introduction

Pancragen is the pancreatic member of the Khavinson bioregulator series — four residues, Lys-Glu-Asp-Trp, carried as a C-terminal amide — and it is the only compound in this batch that has been given to monkeys.

That is a small distinction and a real one. Almost all of the evidence in this family stops at the cell-culture dish or the rat. Two reports from a primate centre describe glucose tolerance testing in old female rhesus macaques, one of them a head-to-head comparison against glimepiride, a licensed sulfonylurea ^{[6, 5]}. A primate model of age-related glucose intolerance is closer to human physiology than anything else this series has been tested in.

The usual limitations still hold and are stated once here rather than under each heading. Every study traces to the St Petersburg Institute of Bioregulation and Gerontology or its collaborators. Several are published only in Russian in gerontology journals with limited circulation. Group sizes are small — nine animals split across two arms in the primate comparison, 33 participants in the single human report. Nothing has been independently replicated. And this compound carries one problem of its own: the published record is inconsistent about whether the material studied was the amide or the free acid.

What Is Pancragen?

A synthetic tetrapeptide, written KEDW in single-letter code and specified in the most precise source as H-Lys-Glu-Asp-Trp-NH2 — that is, with the C-terminal carboxyl replaced by an amide ^[1].

The amidation makes this the structural odd one out of the series. Every other compound in this batch is an unmodified peptide with a free C-terminal carboxyl. Amidation removes a negative charge, raises the isoelectric point, and typically increases resistance to carboxypeptidases — three changes that would matter to any account of how the molecule survives and where it goes. The literature does not treat it consistently: the 2007 rat paper states the amide explicitly, a 2012 cross-tissue differentiation study writes the bare sequence ^[3], and the originating group's own 2022 review lists the compound as KEDW-NH2 ^[8]. The two forms differ by 0.98 daltons and are different substances.

In the series' design logic this peptide corresponds to a pancreatic polypeptide complex, and its research programme is entirely endocrine-pancreatic. It 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.

Pancragen Specifications

The formula and mass above are PubChem's record for compound identifier 68451868, the C-terminal amide of the tetrapeptide, written H-Lys-Glu-Asp-Trp-NH2. The amide is not an incidental detail: this is the only C-terminally amidated member of the bioregulator series, and the free-acid tetrapeptide is a different substance with a mass 0.98 daltons higher. The published literature is inconsistent about it — a 2007 rat study specifies the amide explicitly, a 2012 differentiation study writes the sequence without it, and the originating group's 2022 transporter review lists the compound as KEDW-NH2. Where a paper does not state which form was used, this page does not assume. No CAS registry number and no FDA/NCATS unique ingredient identifier resolve for either form, so both fields are published as unknown rather than estimated.

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 Pancragen Work?

Not established, and the proposed account stops one step short of a mechanism.

What is proposed. In ageing cultures of pancreatic cells the tetrapeptide was reported to raise expression of transcription factors that direct differentiation of the two pancreatic lineages: Pdx1 and Ptf1a for acinar cells, and Pdx1, Pax6, Pax4, Foxa2 and Nkx2.2 for islet cells. The authors conclude that these transcription factors are the pharmacological target of the compound ^[2].

Why that is a conclusion and not an observation. A transcription factor whose expression rises after exposure is downstream of whatever the peptide actually did. Calling it a target names the endpoint, not the interaction. No binding partner has been identified for this tetrapeptide, no receptor has been proposed, and no structural or biophysical work on it has been located.

The route problem, which is more interesting than it looks. In the rat diabetes study the two routes tested gave different results: oral administration produced the reported effect on blood glucose, while intramuscular administration normalised adhesion at the mesenteric capillary endothelium and did not modify capillary permeability ^[1]. Two routes producing two different effects in one experiment is a finding about disposition that nobody has followed up. No pharmacokinetic dataset exists for this compound in any species.

Preclinical Research on Pancragen

Animal research

Glucose tolerance in old rhesus monkeys

The comparison against glimepiride. Nine clinically healthy old female rhesus macaques, aged 20 to 25 years, were divided between two arms: five received 0.05 mg per animal daily by intramuscular injection for ten days, and four received 4 mg of oral glimepiride daily for the same period. Blood was sampled before, during and after administration, both under basal conditions and during glucose tolerance testing, for glucose, insulin and C-peptide ^[5].

Both compounds lowered basal blood glucose. The tetrapeptide also normalised plasma insulin and C-peptide levels in response to glucose. Glimepiride produced a more pronounced and more delayed glucose-lowering effect and stimulated C-peptide secretion without significantly affecting insulin ^[5].

The earlier report. Old animals showed a reduced rate of glucose clearance and higher insulin and C-peptide peaks at 5 and 15 minutes after a glucose load than young animals. Administration of 50 µg per animal daily for ten days markedly raised the clearance rate and normalised the insulin and C-peptide response, and the effect partly persisted three weeks after administration stopped ^[6].

How much weight this carries. Real strengths: a primate model, an age-matched physiological deficit, an objective and well-standardised endpoint, an active comparator, and a persistence measurement. Real limits: five animals in the treated arm, no placebo arm, no blinding described, no randomisation described, one laboratory, and Russian-language publication. The persistence finding in particular — an effect outlasting administration by three weeks — is the kind of result that would need independent replication before it could be relied on at all.

Streptozotocin-induced diabetes in rats

Wistar rats with streptozotocin-induced diabetes received the amidated tetrapeptide. Oral administration produced a pronounced glucose-lowering effect during the period of administration. Intramuscular administration normalised adhesion of the mesenteric capillary endothelium but did not change capillary permeability ^[1]. The authors describe the results as homeostatic and endothelioprotective in the early period of the disease — a deliberately bounded claim, and the boundary is part of the finding.

Organotypic pancreatic explants

Explants of pancreas from 3-week-old and 18-month-old rats were exposed at 0.05 ng/ml; growth was stimulated relative to control explants in both age groups, and the same experiment reported the corresponding tissue-matched effects for three sibling peptides in heart, lung and prostate ^[7].

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

Pancragen Mechanism of Action

In vitro research

Differentiation transcription factors in ageing pancreatic cells. Expression of differentiation markers fell as pancreatic cell cultures aged. The tetrapeptide raised expression of Pdx1 and Ptf1a in acinar cells and of Pdx1, Pax6, Pax4, Foxa2 and Nkx2.2 in islet cells, in both young and aged cultures ^[2].

Tissue matching across three cell types. In a cross-comparison, late-passage cultures of human embryonic pancreatic cells, human bronchial cells and human prostatic fibroblasts all showed reduced differentiation markers. This tetrapeptide raised CXCL12 and Hoxa3 in the pancreatic cells, while Bronchogen acted on the bronchial cells and Vesugen on the fibroblasts ^[3]. The reported effect was larger in aged cultures than young ones in every case, which the authors propose as the basis of a geroprotective effect.

Findings in this section were obtained in cell culture and in excised tissue. Nothing in them establishes anything about intact animals or about humans.

What Is Pancragen Being Researched For?

• Age-related decline in endocrine pancreatic function — glucose clearance, insulin and C-peptide dynamics in old primates ^{[6, 5]}.
• Experimental diabetes mellitus in rodents — blood glucose and capillary endothelial behaviour ^[1].
• Pancreatic cell differentiation — the transcription-factor work in ageing culture ^[2].
• Carbohydrate metabolism in older people with type 2 diabetes mellitus — the single human report ^[4].

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

Human Research on Pancragen

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

One report has been identified.

Design as described. Two groups of older people were examined: 30 described as healthy and 33 with type 2 diabetes mellitus. Nocturnal melatonin production was measured and found to be significantly lower — by 70% — in the group with diabetes than in age-matched healthy participants. Within the diabetes group, some participants received the tetrapeptide and some did not ^[4].

Results as reported. In participants with diabetes who received the tetrapeptide, fasting glucose fell significantly, as did glucose during a standard tolerance test, plasma insulin concentration and the insulin resistance index. In participants who did not receive it, no change in carbohydrate metabolism indices was observed. The authors conclude that disturbed melatonin-producing function of the pineal gland contributes to insulin resistance in older people, and describe the tetrapeptide as a promising approach ^[4].

Limitations. The report is not described as randomised, blinded or placebo-controlled, and the indexed abstract does not say how participants were allocated to receive the compound or not. It gives no effect sizes and no confidence intervals. The melatonin observation and the glucose observation are separate findings joined by an interpretation, not by an experiment: nothing in the design tests whether the reported metabolic change ran through melatonin. And 33 participants split across two conditions is small for a metabolic endpoint with this much day-to-day variability.

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.

Pancragen vs Related Compounds

Bronchogen and Vesugen :: The two peptides tested beside this one in the tissue-matching experiment, each reported to act on its own cell type ^[3]. The design of that study is the clearest statement of the series' tissue-specificity premise available anywhere in its literature. Cardiogen, Prostamax and Bronchogen :: Tested alongside this one in organotypic explants of heart, prostate, lung and pancreas from young and old rats, each matched to its own tissue ^[7]. Livagen :: Lys-Glu-Asp-Ala. The nearest structural neighbour in the series — the same three N-terminal residues with alanine in place of tryptophan — and positioned against liver rather than pancreas. That a single terminal-residue change is held to redirect the compound to a different organ is the series' premise in its strongest form, and it has not been tested against a scrambled or single-substitution control in the published work located here.

Against licensed antidiabetic pharmacology

The primate comparison against glimepiride is the only head-to-head against an approved medicine anywhere in this batch ^[5]. Four animals received the comparator. The comparison is a description, not a trial.

Evidentiary position

Not approved by the U.S. Food and Drug Administration, no registered trial, one non-randomised human report.

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

Chemical & Molecular Characteristics

The amide is the defining feature. PubChem compound identifier 68451868 is the C-terminal amide, C26H37N7O8, average mass 575.60 g/mol. The free acid is a separate substance 0.98 daltons heavier. A mass spectrum resolves the two easily; the problem is not measurement but specification, because a paper or a certificate that writes only "KEDW" has not said which substance it means.

Tryptophan gives this compound an analytical advantage the rest of the series lacks. The indole ring absorbs strongly near 280 nm, so ultraviolet quantification does not have to rely on peptide-bond absorbance near 214 nm where buffers interfere. It also confers real reversed-phase retention on a molecule that would otherwise be dominated by its two acidic side chains, so a purity figure by HPLC carries more information here than for the polar tripeptides of this family.

Tryptophan is also the degradation route. The indole is the most oxidation-sensitive standard side chain, giving oxindolylalanine, N-formylkynurenine and kynurenine products at mass shifts of +16, +32 and +4 daltons. Light and residual oxidants drive it. Because the residue sits at the C-terminus and is amidated, oxidation there changes both the chromophore the material is quantified by and the terminus that the amidation was presumably intended to protect.

Aspartate and glutamate bring isomerisation of identical mass. Both residues undergo the alpha/beta and alpha/gamma rearrangements characteristic of Asp- and Glu-containing peptides. The rearranged products have the same molecular formula and the same mass as the intended compound. Composition confirmed by mass spectrometry is not sequence confirmed, and for a peptide whose claimed activity is attributed to one specific four-residue arrangement, that gap is the one worth closing with a sequencing method.

Two register fields are empty and stay empty. No CAS registry number and no FDA/NCATS unique ingredient identifier resolve for either form of this compound. They are shown as unknown above rather than filled with a number belonging to something else.

Frequently Asked Questions

Scientific References

1. Khavinson VKh, Gavrisheva NA, Malinin VV, et al.. Effect of pancragen on blood glucose level, capillary permeability and adhesion in rats with experimental diabetes mellitus Bulletin of experimental biology and medicine; 2007. PMID 18642713 doi:10.1007/s10517-007-0377-3
2. Khavinson VKh, Durnova AO, Polyakova VO, et al.. Effects of pancragen on the differentiation of pancreatic cells during their ageing Bulletin of experimental biology and medicine; 2013. PMID 23486591 doi:10.1007/s10517-013-1987-6
3. Khavinson VKh, Linkova NS, Polyakova VO, et al.. Peptides tissue-specifically stimulate cell differentiation during their aging Bulletin of experimental biology and medicine; 2012. PMID 22808515 doi:10.1007/s10517-012-1664-1
4. Korkushko OV, Khavinson VKh, Shatilo VB, et al.. Prospects of using pancragen for correction of metabolic disorders in elderly people Bulletin of experimental biology and medicine; 2011. PMID 22448364 doi:10.1007/s10517-011-1354-4
5. Goncharova ND, Ivanova LG, Oganyan TE, et al.. [Correction of impaired glucose tolerance using tetrapeptide (Pancragen) in old female rhesus monkeys] Advances in gerontology = Uspekhi gerontologii; 2015. PMID 28509500
6. Goncharova ND, Ivanova LG, Oganian TÉ, et al.. [Impact of tetrapeptide pancragen on endocrine function of the pancreas in old monkeys] Advances in gerontology = Uspekhi gerontologii; 2014. PMID 25946840
7. Zakutskiĭ AN, Chalisova NI, Ryzhak GA, et al.. [The tissue-specific effect of synthetic peptides-biologic regulators in organotypic tissues culture in young and old rats] Advances in gerontology = Uspekhi gerontologii; 2006. PMID 17152728
8. Khavinson V, Linkova N, Kozhevnikova E, et al.. Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers International journal of molecular sciences; 2022. PMID 35887081 doi:10.3390/ijms23147733

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.