# Pancragen

> Pancragen is a synthetic tetrapeptide bioregulator with the amino-acid sequence Lys-Glu-Asp-Trp (KEDW), supplied for research by the St. Petersburg Institute of Bioregulation and Gerontology. It has been studied in pancreatic cell cultures, diabetic rat models and aged rhesus monkeys, with a focus on glucose regulation. Human data come from one small study in older adults, and pancragen is not FDA approved.

Canonical: https://peptideproperties.com/compounds/pancragen/

## Identity

- **Class:** Short Peptide Bioregulators
- **Also known as:** Lys-Glu-Asp-Trp
- **Sequence notes:** Published as Lys-Glu-Asp-Trp (KEDW). Two rat studies describe the C-terminal amide form (Lys-Glu-Asp-Trp-NH2); other studies do not specify the terminal group, and no PubChem record was available to confirm the free-acid form.

## Key facts

- Class: short peptide bioregulator (synthetic tetrapeptide)
- Sequence: Lys-Glu-Asp-Trp (KEDW); some studies describe a C-terminal amide
- Origin: St. Petersburg Institute of Bioregulation and Gerontology, Russia
- Research focus: pancreatic cell differentiation and glucose regulation
- Evidence: cell culture, rat and rhesus monkey studies, plus one small human study
- No PubChem compound record identified; formula and molecular weight not listed here
- Regulatory status: not approved by the FDA for any use

## What Is Pancragen?

Pancragen is a synthetic tetrapeptide, Lys-Glu-Asp-Trp, studied as a short peptide bioregulator with activity directed at pancreatic tissue[1][2]. The material used in primate research was supplied by the St. Petersburg Institute of Bioregulation and Gerontology[3].Short peptide bioregulators are di-, tri- and tetrapeptides that researchers in this program have tested for tissue-specific effects. In a study comparing several of them in human embryonic cell cultures, pancragen raised expression of differentiation factors in pancreatic cells, while bronchogen acted on bronchial epithelial cells and vesugen on prostatic fibroblasts[2].The indexed literature on pancragen is small and appears mainly in Bulletin of Experimental Biology and Medicine and Advances in Gerontology. It spans cell and tissue culture, rat models of diabetes, aged rhesus monkeys, biophysical binding studies and a single clinical study in older adults[4].

## Chemical Structure and Molecular Identity

Pancragen is a linear tetrapeptide of lysine, glutamic acid, aspartic acid and tryptophan, written Lys-Glu-Asp-Trp or KEDW in one-letter code[5]. Two rat studies describe it specifically as the C-terminal amide, Lys-Glu-Asp-Trp-NH2[6][7], while other papers give only the residue sequence.No PubChem compound record for pancragen was identified, so this page does not list a molecular formula, molecular weight, CAS number or InChIKey. The free-acid and C-terminal amide forms differ in formula and mass, which matters when comparing studies or analytical data.PositionResidueSide-chain character1 (N-terminus)Lysine (K)Basic, positively charged2Glutamic acid (E)Acidic, negatively charged3Aspartic acid (D)Acidic, negatively charged4 (C-terminus)Tryptophan (W)Aromatic, hydrophobicThe central Glu-Asp pair recurs in other peptides from the same research program, including bronchogen (Ala-Glu-Asp-Leu) and vesugen (Lys-Glu-Asp)[2].

## Research History and Development

Pancragen appears in the indexed literature from 2006, starting with tissue-culture work and extending to diabetes models, primates and a human study by the mid-2010s. Nine of the ten papers reviewed for this page list V. Kh. Khavinson as a co-author.A 2006 organotypic culture study tested pancragen alongside cardiogen, bronchogen and prostamax on explants of heart, lung, prostate and pancreas from young (3-week-old) and aged (18-month-old) rats, reporting a stimulating effect in the matching tissue cultures[8]. A 2007 study then examined the amidated tetrapeptide in Wistar rats with streptozotocin-induced diabetes[6].From 2011 onward, work extended to a clinical study in older adults with and without type 2 diabetes[4], cell-culture studies of pancreatic differentiation markers[1], and two studies in aged female rhesus monkeys[5][3]. Parallel biophysical papers examined how the tetrapeptide might interact with histones and DNA[9][10].

## Mechanisms Studied in Research

Proposed mechanisms center on transcription factors that control pancreatic cell differentiation and on direct interactions of the peptide with chromatin. These proposals rest on a small number of in-vitro and computational studies.
### Pancreatic differentiation factors
In cultured pancreatic cells, pancragen increased expression of differentiation factors for acinar cells (Pdx1, Ptf1a) and for islet of Langerhans cells (Pdx1, Pax6, Pax4, Foxa2, Nkx2.2) in both young and aged cultures; the authors proposed this as a mechanism behind effects seen in animal models[1]. In human embryonic pancreatic cells, it also stimulated CXCL12 and Hoxa3 expression, with a more pronounced effect in late-passage (aging) cultures[2].
### Histone and DNA interactions
Fluorescence-quenching experiments indicated that Lys-Glu-Asp-Trp, along with several other short peptides, binds wheat histones H1, H2B, H3 and H4, apparently at N-terminal histone regions[9]. A molecular-mechanics study suggested the tetrapeptide can interact with both the minor and major grooves of DNA and proposed the sequence GGCAG as a putative binding site[10]. That paper also described the tetrapeptide as a mimetic of insulinotropic peptides; a specific receptor is not identified in the abstracts reviewed.
### Pineal and melatonin link
In the clinical study, nocturnal melatonin production was markedly reduced in older adults with type 2 diabetes. The authors interpreted this as evidence that impaired pineal melatonin output contributes to insulin resistance in aging, and they framed pancragen as one approach to correcting that resistance[4]. The abstract does not report whether pancragen itself changed melatonin levels.
### Apoptosis markers
A 2010 study evaluated the amidated peptide using metabolic parameters of apoptosis across ontogeny and in streptozotocin-induced diabetes, which the authors used as a model of accelerated aging[7]. Its abstract does not report specific results.

## Key Findings From Published Studies

Published studies report lower blood glucose and normalized insulin dynamics in diabetic rats, aged monkeys and older adults with type 2 diabetes. Group sizes were small and the work comes largely from one research network.ModelMain reported outcomePancreatic cell cultures (in vitro)Higher expression of acinar and islet differentiation factors[1]Rats with streptozotocin-induced diabetesLower blood glucose; normalized capillary endothelial adhesion[6]Aged female rhesus monkeysFaster glucose clearance; normalized insulin and C-peptide dynamics[5]Older adults with type 2 diabetesLower fasting glucose, insulin and insulin resistance index[4]
### Rat models
In Wistar rats with streptozotocin-induced diabetes, oral pancragen produced a pronounced hypoglycemic effect during treatment, while intramuscular administration normalized adhesion of the mesenteric capillary endothelium without changing capillary permeability[6]. Earlier explant work reported tissue-specific stimulation of pancreatic cultures from both young and aged rats[8].
### Rhesus monkey studies
In aged female rhesus monkeys, baseline glucose tolerance tests showed slower glucose clearance and higher insulin and C-peptide peaks than in young animals. After a course of pancragen, the glucose disappearance rate increased and insulin and C-peptide dynamics normalized, with the effect partly persisting three weeks after treatment stopped[5].A follow-up study in nine old females compared pancragen (five animals) with the hypoglycemic drug glimepiride (four animals). Both lowered basal glucose. Pancragen also normalized insulin and C-peptide levels, whereas glimepiride produced a stronger, delayed hypoglycemic effect and stimulated C-peptide secretion without a significant effect on insulin secretion[3].
### Human data
One study examined 30 healthy older adults and 33 older adults with type 2 diabetes. Nocturnal melatonin production was about 70% lower in the diabetes group. Among patients with type 2 diabetes, pancragen was associated with lower fasting and glucose-tolerance-test glucose, lower plasma insulin and a lower insulin resistance index, while patients not receiving it showed no change[4]. The abstract does not describe randomization or blinding.Because studies differ on pancragen's C-terminal form, mass spectrometry and HPLC data on a certificate of analysis help confirm which molecule a sample contains.

## Regulatory and Research Status

Pancragen is not approved by the U.S. Food and Drug Administration for any medical use and remains an investigational research compound. Its clinical evidence consists of a single small study in older adults[4].Statements in the source abstracts that pancragen is effective and safe, or a promising tool for diabetes and pancreatitis, are the authors' conclusions from small studies[3][1]. They are not regulatory findings, and no large controlled trials appear in the literature reviewed here.Open questions for laboratory work include the exact terminal form of the material used in each study, the lack of a defined molecular target, and limited replication outside the originating research group.

## FAQ

**What is pancragen?**
Pancragen is a synthetic tetrapeptide, Lys-Glu-Asp-Trp, classed as a short peptide bioregulator. Research material has been supplied by the St. Petersburg Institute of Bioregulation and Gerontology in Russia, and it has been studied in pancreatic cell cultures, rats with experimental diabetes, aged rhesus monkeys and one small study in older adults. Research has focused on glucose regulation and pancreatic cell differentiation markers.

**What is the amino acid sequence of pancragen?**
Pancragen is reported as Lys-Glu-Asp-Trp, or KEDW in one-letter code. It contains lysine, glutamic acid, aspartic acid and tryptophan. Two rat studies describe the compound as a C-terminal amide (Lys-Glu-Asp-Trp-NH2), while other papers list only the residues, so the terminal form of a given material should be checked by analytical testing.

**Is pancragen FDA approved?**
No. Pancragen is not approved by the U.S. Food and Drug Administration for any medical use. Its published evidence comes mostly from cell culture, rat and monkey studies, plus a single small clinical study in older adults with and without type 2 diabetes. It is regarded as an investigational research compound.

**What does the research on pancragen show?**
Published studies report that pancragen lowered blood glucose in rats with streptozotocin-induced diabetes, improved glucose clearance and normalized insulin and C-peptide dynamics in aged rhesus monkeys, and was associated with lower glucose and insulin resistance in a small group of older adults with type 2 diabetes. In cell cultures it increased pancreatic differentiation factors. Studies were small and largely from one research group.

**How is pancragen different from bronchogen?**
Both are tetrapeptides from the same short peptide bioregulator program and share a central Glu-Asp pair. Pancragen is Lys-Glu-Asp-Trp and has been studied for pancreatic effects, while bronchogen is Ala-Glu-Asp-Leu and has been studied in bronchial and lung models. In one cell-culture comparison, each stimulated differentiation factors only in its matching tissue type.

**Has pancragen been tested in humans?**
Only in one small published study. It included 30 healthy older adults and 33 older adults with type 2 diabetes. In the diabetes group, pancragen was associated with lower fasting glucose, lower insulin levels and a lower insulin resistance index. The abstract does not describe randomization or blinding, so the findings are preliminary.

## References

1. 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
2. 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
3. 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
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
5. 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
6. 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
7. Khavinson VKh, Gapparov MM, Sharanova NE, et al. Study of biological activity of Lys-Glu-Asp-Trp-NH2 endogenous tetrapeptide. Bulletin of experimental biology and medicine 2010. PMID: 21246099
8. 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
9. Fedoreyeva LI, Smirnova TA, Kolomijtseva GY, et al. Interaction of short peptides with FITC-labeled wheat histones and their complexes with deoxyribooligonucleotides. Biochemistry. Biokhimiia 2013. PMID: 23581987
10. Tarnovskaya SI, Yakutseni PP, Khavinson VKh. Study of interactions between DNA and tetrapeptides using methods of molecular mechanics. Bulletin of experimental biology and medicine 2014. PMID: 24770759