Pancragen
Also known as: KEDW · KEDWa · Lys-Glu-Asp-Trp · H-Lys-Glu-Asp-Trp-NH2 · Pancragene · pancreas peptide bioregulator
Research focus
Pancreas and endocrine/metabolic (carbohydrate) regulation — aging-related glucose tolerance
US regulatory status
Not FDA-approved · Not compoundable
Evidence rating
Theoretical
Origin
Pancragen is a synthetic tetrapeptide developed by the Khavinson group at the St. Petersburg Institute of Bioregulation and Gerontology (Russia). It is one of the "Cytogen" family of short synthetic peptides — designed sequences intended to mimic fragments the group identified within longer tissue extracts (the older "Cytomax" peptide preparations). According to the originating publications, the team analyzed the amino-acid sequences of insulinotropic polypeptides, identified a shared four-residue fragment, and synthesized the protease-resistant amidated analog (H-Lys-Glu-Asp-Trp-NH2, "KEDWa") so that it could survive gastrointestinal enzymes. The work sits within the institute's broader peptide-bioregulator and gerontology program led by V.Kh. Khavinson, with collaborators including G.A. Ryzhak, I.M. Kvetnoy, N.S. Linkova, S.I. Tarnovskaya, and (for the primate and human work) N.D. Goncharova and the Kiev/Ukraine gerontology group of O.V. Korkushko.
Plain-language summary
Pancragen is a lab-made four-amino-acid peptide (Lys-Glu-Asp-Trp) from a Russian gerontology institute, marketed as a "pancreas support" bioregulator. The published research is almost entirely preclinical — diabetic rats, aged monkeys, and cells in a dish — and nearly all of it comes from one research group. In those experiments the peptide reportedly nudged blood-sugar and insulin measures toward normal. There is one small, short, unblinded human study in older adults with type 2 diabetes, but no large, controlled, independently replicated human trial. In plain terms: there is an interesting preclinical story, very thin human data, and a lot still unproven. It is not an approved medicine in the U.S.
Claimed mechanism (as reported)
The originating group proposes that Pancragen acts as a "gene-regulatory" peptide: published in-silico and in-vitro work from the Khavinson group reports that the tetrapeptide can interact with DNA (modeling suggests a putative GGCAG/major-groove binding site near the preproinsulin promoter) and with histone N-terminal regions, and reportedly up-regulates pancreatic differentiation and functional-activity markers (e.g., Pdx1, Pax4/Pax6, Foxa2, Nkx2.2, PCNA, Ki67) while lowering pro-apoptotic p53 in cultured cells. The proposed downstream effect is restoration of insulin/C-peptide dynamics and reduced blood glucose. This mechanism is a hypothesis from a single research program — supported mainly by molecular-modeling and cell-culture data — and has not been independently confirmed in humans.
Evidence summary
Small, single-group body of literature. The published record is dominated by Khavinson-group preclinical work: streptozotocin/alloxan diabetic rats, aged rhesus monkeys, and in-vitro pancreatic cell cultures, plus molecular-modeling papers on DNA/histone interaction. Reported effects include lowered blood glucose, partial normalization of insulin/C-peptide responses, and up-regulation of pancreatic differentiation markers. Human evidence is essentially limited to a single small, open-label, unblinded study (~33 older type-2-diabetic patients plus 30 healthy elderly controls) from the originating/collaborating group; there are no large, randomized, placebo-controlled, independently replicated human trials in the peer-reviewed English-language literature as of 2026. Because the human signal rests on one uncontrolled study and the mechanism is supported chiefly by in-silico and cell-culture work, TPC grades this "No Human Data" in the sense that no controlled clinical efficacy evidence exists — and flags the one open-label report explicitly so readers are not misled in either direction.
What the research reports
Effect of tetrapeptide on insulin biosynthesis in rats with alloxan-induced diabetes; Effect of pancragen on blood glucose level, capillary permeability and adhesion in rats with experimental diabetes mellitus
Grade DKhavinson VKh; Gavrisheva NA, Malinin VV, Chefu SG et al. · Bulletin of Experimental Biology and Medicine · 2005-2008
Reported finding: Oral or intramuscular tetrapeptide reportedly produced a hypoglycemic effect, partially restored insulin synthesis, and improved capillary endothelial adhesion in chemically-diabetic rats. Reported as preliminary, without independent replication.
Sample: Small rodent cohorts (group sizes typically n=10-20 per arm; not always reported)
Methodology: D - small rodent diabetes models (streptozotocin/alloxan), single research group, no blinding
Limitations: Animal models of chemically-induced diabetes; small samples; unblinded; single originating group; surrogate biochemical endpoints rather than clinical outcomes.
Impact of tetrapeptide pancragen on endocrine function of the pancreas in old monkeys; Correction of impaired glucose tolerance using tetrapeptide (Pancragen) in old female rhesus monkeys
Grade DGoncharova ND, Ivanova LG, Oganyan TE, Vengerin AA, Khavinson VKh · Advances in Gerontology (Uspekhi Gerontologii) · 2014-2015
Reported finding: Over a 10-day intramuscular course (~50 micrograms/animal/day), Pancragen reportedly increased the glucose 'disappearance' rate and normalized insulin and C-peptide dynamics on glucose tolerance testing in old monkeys, with some effect persisting ~3 weeks after withdrawal. Reported as promising by the authors.
Sample: n=9 aged rhesus females total (5 Pancragen, 4 comparator glimepiride)
Methodology: D - very small non-human-primate study (single-digit n per group), open design
Limitations: Extremely small sample; not blinded; single research collaboration; comparator (glimepiride) actually produced a stronger glucose-lowering effect; surrogate endpoints.
Prospects of using pancragen for correction of metabolic disorders in elderly people
Grade CKorkushko OV, Khavinson VKh, Shatilo VB, Antonyk-Sheglova IA, Bondarenko EV · Bulletin of Experimental Biology and Medicine · 2011
Reported finding: In the type-2-diabetes subgroup, pancragen was reported to lower fasting and post-load glucose and reduce plasma insulin and an insulin-resistance index; the authors linked this to reduced nocturnal melatonin in diabetics. This is the principal human report and is uncontrolled. Reported without independent replication.
Sample: 63 older adults total (33 with type 2 diabetes, 30 healthy elderly)
Methodology: C/D - single small open-label human study, no placebo arm, single research group
Limitations: Open-label, no randomization or placebo, small sample, single originating/collaborating group, short duration; cannot establish efficacy.
Effects of pancragen on the differentiation of pancreatic cells during their ageing; Study of interactions between DNA and tetrapeptides using methods of molecular mechanics
Grade DKhavinson VKh, Durnova AO, Polyakova VO, Linkova NS, Tarnovskaya SI, Kvetnoy IM et al. · Bulletin of Experimental Biology and Medicine · 2012-2014
Reported finding: Reported tissue-specific up-regulation of pancreatic differentiation and proliferation markers (Pdx1, Pax4/Pax6, Foxa2, Nkx2.2, PCNA, Ki67) and down-regulation of p53 in cultured cells; molecular-mechanics modeling proposed a putative DNA major-groove (GGCAG) binding site. Offered as the proposed mechanism.
Sample: In-vitro 'young' vs 'aged' human/embryonic pancreatic cell cultures; computational docking (no subjects)
Methodology: D - in-vitro cell culture and in-silico molecular modeling only; mechanistic, not clinical
Limitations: Cell-culture and computational work cannot demonstrate clinical effect; mechanism is a single-group hypothesis; no independent confirmation; risk of overinterpretation of in-silico binding.
Administration reported in studies
In the published preclinical work the tetrapeptide was given either orally or by intramuscular injection. Rodent studies used short courses; the aged-monkey studies used roughly 50 micrograms per animal per day intramuscularly for about 10 days. The single small human report used a short oral/parenteral course of the peptide bioregulator in older adults. Doses, routes, and durations vary across papers and are described inconsistently. This is a summary of research conditions — not a dosing recommendation and not a protocol endorsed by TPC.
This section reports what published studies describe. It is not a dosing recommendation from TPS.
Safety record
No formal human safety database, no pharmacovigilance reporting, and no published long-term toxicology in humans exist for Pancragen. The originating papers describe the peptide as well tolerated in their small animal and single open-label human study, but those reports were not designed or powered to detect adverse events, and no independent safety evaluation has been published. Material sold online as a "research chemical" is unregulated, of unverified identity and purity, and may be contaminated or mislabeled. TPC makes no safety claim; absence of reported harm in tiny studies is not evidence of safety.
US legal status
Not FDA-approved for any use. Not on the FDA 503A compoundable bulk drug substances list, and not legally compoundable for human clinical use in the United States. It has no recognized status as a dietary supplement. It is sold online only as a "research chemical" / "for research use only" product; vendors in that channel are unregulated and are not verified by TPC. Nothing here should be read as endorsing personal use.
Open research questions
- ? Has any of the reported glucose-lowering or insulin-normalizing effect ever been replicated by a research group independent of Khavinson and his named collaborators?
- ? Does Pancragen show benefit in a properly randomized, double-blind, placebo-controlled human trial — and against an active comparator, given that glimepiride outperformed it in the monkey study?
- ? What is the actual human pharmacokinetics and bioavailability of an orally administered tetrapeptide, and does meaningful intact peptide reach any target tissue?
- ? Is the proposed DNA/histone gene-regulatory mechanism real and tissue-specific in vivo, or an artifact of in-silico docking and high-concentration cell culture?
- ? What does long-term human safety look like, since no toxicology, pharmacovigilance, or controlled safety data exist?
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