Pancragen

A synthetic amidated tetrapeptide (Lys-Glu-Asp-Trp-NH2) from the Khavinson bioregulator program, attributed to the pancreas and studied in rodent, primate, and one small Ukrainian clinical report for glucose tolerance and islet-cell gene expression.

Also referenced as: KEDW, KEDWa, Lys-Glu-Asp-Trp, Lys-Glu-Asp-Trp-NH2, H-Lys-Glu-Asp-Trp-NH2, Pancragene, Pankragen

Also appears in: Longevity

What is Pancragen?

Pancragen is a synthetic tetrapeptide with the sequence Lys-Glu-Asp-Trp, usually supplied as the C-terminal amide (Lys-Glu-Asp-Trp-NH2, abbreviated KEDW or, in the founding paper, KEDWa), developed at the Saint Petersburg Institute of Bioregulation and Gerontology as the pancreas-attributed member of Vladimir Khavinson’s short-peptide bioregulator family. According to the originating paper, the sequence was not isolated from pancreatic tissue but chosen because a four-residue motif recurred across insulinotropic polypeptides, and the amidated analog was synthesized to resist gastrointestinal proteases; later papers from the same group nonetheless describe it as an “endogenous” or “natural” tetrapeptide. It appears in the research-peptide market alongside Livagen, Cartalax, Cardiogen, and Pinealon as the metabolic entry in that line, and in Russia it is sold as an oral dietary supplement rather than a registered drug.

How it works

The proposed mechanism follows the Khavinson bioregulation model, in which short peptides are said to enter the nucleus and alter tissue-specific gene expression. For Pancragen the specific claims are:

• Islet and acinar differentiation-factor expression — in cultures of human pancreatic cells, KEDW increased expression of the transcription factors Pdx1 and Ptf1a in acinar cells and Pdx1, Pax6, Pax4, Foxa2, and Nkx2.2 in islet cells, with the effect reported in both early-passage and late-passage (“aged”) cultures (Khavinson et al., Bulletin of Experimental Biology and Medicine, 2013, 154(4):501–504). An earlier paper from the same group reported tissue-specific induction of CXCL12 and Hoxa3 in pancreatic cells but not in bronchial cells or prostatic fibroblasts, where the sister peptides Bronchogen and Vesugen were active instead (Khavinson et al., Bulletin of Experimental Biology and Medicine, 2012, 153(1):148–151)
• Promoter methylation changes — in aging pancreatic cell cultures, KEDW treatment was associated with altered CpG methylation at the PDX1, PAX6, and NGN3 promoters in step with expression changes, while PAX4 methylation did not change and FOXA2 methylation changed without tracking expression, which the authors took as evidence that only some of the peptide’s expression effects run through methylation (Ashapkin et al., Biochemistry (Moscow), 2015, 80(3):310–322)
• Proposed direct DNA binding — the original hypothesis was that KEDW activates the preproinsulin promoter by complementary interaction with the GGCAGG/CCTGCC sequence (Khavinson, Bulletin of Experimental Biology and Medicine, 2005, 140(4):452–454). Molecular-mechanics modeling later suggested the peptide could occupy the major groove of DNA at a GGCAG site (Tarnovskaya et al., Bulletin of Experimental Biology and Medicine, 2014, 156(5):689–693), but a subsequent docking survey of 19 short peptides from the same group assigned KEDW to an ACCT motif instead (Khavinson et al., Bulletin of Experimental Biology and Medicine, 2016, 162(2):288–292), so the group’s own models do not agree on the target sequence. A fluorescence-quenching study reported binding to wheat histone tails (Fedoreyeva et al., Biochemistry (Moscow), 2013, 78(2):166–175). These are computational and in-vitro observations; no study has shown KEDW bound to a human promoter in intact cells
• Insulin biosynthesis and endothelial effects in diabetic rodents — in alloxan-diabetic rats the peptide partially restored insulin synthesis and flattened the glucose curve toward that of normal animals (Khavinson, 2005, above); in streptozotocin-diabetic Wistar rats oral dosing lowered blood glucose during treatment while intramuscular dosing normalized mesenteric capillary endothelial adhesion without changing permeability (Khavinson et al., Bulletin of Experimental Biology and Medicine, 2007, 144(4):559–562)

Research status

Every indexed experimental study on Pancragen comes from the Saint Petersburg Institute of Bioregulation and Gerontology, its parent academy institutes, or collaborators publishing with Khavinson as coauthor (the Kyiv Institute of Gerontology, the Sochi primatology institute, and two Moscow State University groups for the methylation and histone work). A PubMed search for KEDW, Lys-Glu-Asp-Trp, or Pancragen returns no experimental study from an unaffiliated group; the only outside mention is a 2025 materials-science review from IIT Gandhinagar that summarizes the Khavinson cell-culture findings without new data. No replication has been published outside this network, and there is no record of a randomized or blinded trial.

Rodent work (2005–2010). The founding paper described the sequence rationale and reported partially restored insulin synthesis in alloxan-diabetic rats (Khavinson, Bulletin of Experimental Biology and Medicine, 2005, 140(4):452–454). A 2007 morphology study in diabetic rats reported a “regulatory effect” on pancreatic tissue in a two-sentence abstract that gives no numbers (Kvetnoi et al., Bulletin of Experimental Biology and Medicine, 2007, 143(3):368–371, which spells the compound “pancragene”). The streptozotocin-rat study of glucose and capillary endothelium followed the same year (Khavinson et al., 2007, 144(4):559–562), and a 2010 paper evaluated apoptosis-related metabolic markers across ontogeny and in streptozotocin diabetes (Khavinson et al., Bulletin of Experimental Biology and Medicine, 2010, 149(3):351–353). Organotypic explant cultures from young and aged rats showed a stimulating effect at 0.05 ng/mL that the authors characterized as tissue-specific (Zakutskii et al., Advances in Gerontology, 2006, 19:93–96, Russian-language).

Cell-culture work (2012–2015). The differentiation-factor and methylation studies described above are the most specific mechanistic data in the record. A Russian-language companion paper reported that KEDW raised MMP2, MMP9, serotonin, CD79alpha, Mcl1, PCNA, and Ki67 and lowered p53 in aged human pancreatic cell cultures (Khavinson et al., Advances in Gerontology, 2012, 25(4):680–684). None of these papers reports dose-response curves or an inactive control peptide.

Non-human primate work (2014–2015). Two Russian-language papers from the Research Institute of Medical Primatology in Sochi studied old (20–25 year) female rhesus monkeys. Intramuscular Pancragen at 50 µg per animal per day for 10 days increased the glucose disappearance rate and normalized insulin and C-peptide dynamics during a glucose tolerance test, with partial persistence three weeks after withdrawal; the abstract does not state the group size (Goncharova et al., Advances in Gerontology, 2014, 27(4):662–667). A follow-up compared 5 Pancragen-treated animals with 4 given oral glimepiride, reporting lower basal glucose in both groups, normalized insulin and C-peptide in the peptide group, and a stronger, delayed glucose drop with C-peptide stimulation but no insulin change in the glimepiride group (Goncharova et al., Advances in Gerontology, 2015, 28(3):579–585). The only stated treated sample is five animals.

Human data. The one clinical report in PubMed examined 30 healthy older adults and 33 older patients with type 2 diabetes. Patients who received Pancragen showed lower fasting and post-load glucose, lower plasma insulin, and a lower insulin-resistance index, while untreated patients showed no change; the paper’s framing is that reduced nocturnal melatonin in diabetic elderly contributes to insulin resistance (Korkushko et al., Bulletin of Experimental Biology and Medicine, 2011, 151(4):454–456). The abstract does not describe randomization, blinding, placebo, dose, route, or duration, and no follow-up trial has appeared in the fifteen years since. Additional clinical reports exist only in Russian-language monographs and conference material that are not indexed in PubMed.

Regulatory and trial registry status. ClinicalTrials.gov lists no study of Pancragen, KEDW, or Lys-Glu-Asp-Trp-NH2. The compound has no FDA or EMA record and is not an approved drug anywhere; in Russia it is registered as a biologically active food supplement (capsules delivering 100 µg of the “AKS-P” peptide complex per 0.2 g capsule, made by the Academy-affiliated Firma-Vita), not as a medicinal product, so even its home-market status falls short of a drug approval. The one Western regulatory footprint is a US composition-and-method patent on Lys-Glu-Asp-Trp-NH2 for diabetes mellitus (US 7,491,703; Russian priority 2003, granted 2009), which lapsed in 2021 for non-payment of maintenance fees. No approval, filing, or registry entry occurred in 2025 or 2026.

Common dosage forms

• Lyophilized powder in vials — the dominant research-market format, labeled by total peptide mass in the tens of milligrams per vial and intended for reconstitution.
• Oral capsules and tablets — the Russian supplement format, with 100 µg of peptide per capsule in a microcrystalline cellulose, beet sugar, lactose, starch, and polysorbate excipient base. Capsule versions of the Khavinson “cytogen” line are also sold by Western supplement resellers.
• Combination blends — vendors sometimes bundle Pancragen with other short bioregulators (Livagen, Cardiogen, Vesugen, Pinealon) as “organ support” sets; the published studies tested the peptide alone.

Key considerations

• Regulatory status: Research Market, with no path toward approval. Pancragen is a Russian dietary supplement and a US research-market peptide. It has no FDA or EMA review, no registered clinical trial, no investigational new drug record, and no sponsor pursuing one; the US patent that would have anchored a development program was allowed to lapse in 2021. The Research Market status reflects regional supplement registration with no US approval or development program.
• Single-group evidence with no independent replication. Every indexed experimental paper traces to the originating institute and its coauthors, the clinical report is a single open study of 33 patients with no design details in the abstract, and the one primate study that states its numbers treated five animals. Western diabetes and endocrinology literature does not cite the compound. Vendor pages quoting percentage reductions in glucose or insulin requirements are not traceable to the peer-reviewed abstracts.
• The mechanism is a hypothesis, not a demonstrated pathway. Direct peptide-DNA binding rests on docking models and a 2005 conjecture, and the group’s own models name three different target motifs (GGCAGG/CCTGCC in 2005, GGCAG in 2014, ACCT in 2016). The strongest measured effects are changes in transcription-factor expression and promoter methylation in cultured cells, which the authors themselves found inconsistent across genes (PAX4 and FOXA2 did not fit the model). No receptor, transporter, or nuclear-import mechanism has been identified.
• Oral versus injected claims are not interchangeable. The rat study reported glucose lowering with oral dosing and endothelial effects with intramuscular dosing, the primate work was entirely intramuscular, and the Russian product is oral. The amide was chosen for protease resistance, but oral bioavailability of a tetrapeptide has never been measured in humans, so results from one route should not be read onto another.
• Safety data are essentially absent, and the naming is inconsistent. None of the abstracts reports adverse-event collection; the 2015 primate paper asserts safety on the basis of five animals. The compound appears as Pancragen, Pancragene, Pankragen, KEDW, and KEDWa in the literature, and the origin story shifts between a designed analog (2005) and an “endogenous” peptide (2010). It should also not be confused with the pancreas tissue extracts sold under the same program — Pancramin (a bovine pancreas protein and nucleoprotein complex, 10 mg per tablet, registered as a Russian supplement and sold through the Institute’s clinic) and the capsule product marketed as Suprefort or A-1 — which are undefined polypeptide fractions rather than a single defined sequence, and which have no PubMed-indexed studies of their own.