Pancragen

Also known as: KEDW-NH2, Lys-Glu-Asp-Trp-NH2

Evidence: Preclinical

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Overview

Khavinson-series synthetic tetrapeptide (KEDW-NH2) for pancreas; improved glucose tolerance in old rhesus monkeys and diabetic rats, plus one small human study against untreated controls.

Pancragen is a synthetic tetrapeptide (KEDW, Lys-Glu-Asp-Trp), printed with a C-terminal amide in two of the developer's papers (Khavinson 2007; Khavinson 2022). Oral dosing lowered blood glucose in rats with streptozotocin diabetes (Khavinson 2007). In old female rhesus monkeys, 50 mcg per animal daily intramuscularly for 10 days sped glucose clearance and normalized insulin and C-peptide responses, partly lasting 3 weeks (Goncharova 2014). In pancreatic cell cultures it raised Pdx1, Pax6, Pax4, Foxa2 and Nkx2.2 (Khavinson 2013). In 33 older people with type 2 diabetes compared with untreated patients, fasting glucose, insulin and insulin resistance fell (Korkushko 2011); the abstract reports neither randomization nor dose.

Benefits

Better glucose tolerance and insulin dynamics (old rhesus monkeys), lower blood glucose in streptozotocin diabetes (rat, oral), pancreatic differentiation markers (in vitro), lower fasting glucose and insulin resistance (small human study, randomization not reported)

Dosing reference

Research dose: 200 to 1000 mcg daily: vendor/community range, no published human dose. Old monkeys received 50 mcg per animal daily intramuscularly
Range: 200 to 1000 mcg, 1x daily

Sold as oral capsules and as lyophilized powder for injection; vial size (20 mg) is not a dose. Old rhesus monkeys received 50 mcg per animal per day intramuscularly for 10 days (Goncharova 2014). Rats received it orally and intramuscularly (Khavinson 2007). No controlled human glycemic data exist.

Mechanism

Proposed. In young and aged human pancreatic cell cultures it raised transcription factors for acinar (Pdx1, Ptf1a) and islet cell differentiation (Pdx1, Pax6, Pax4, Foxa2, Nkx2.2) (Khavinson 2013), and CXCL12 and Hoxa3 in aged cultures (Khavinson 2012). In diabetic rats intramuscular dosing normalized mesenteric capillary adhesion without changing permeability (Khavinson 2007). How these changes lower glucose is not established, and direct effects on insulin secretion have not been measured in isolated islets.

Evidence

Preclinical: animal or in vitro data only

Oral dosing lowered blood glucose in rats with streptozotocin diabetes; intramuscular dosing normalized capillary adhesion (Khavinson et al., 2007)
At 50 mcg per animal daily intramuscularly for 10 days, sped glucose clearance and normalized insulin and C-peptide in old rhesus monkeys (Goncharova et al., 2014)
Raised acinar and islet differentiation factors (Pdx1, Ptf1a, Pax6, Pax4, Foxa2, Nkx2.2) in pancreatic cell cultures (Khavinson et al., 2013)
Raised CXCL12 and Hoxa3 in aged human pancreatic cell cultures (Khavinson et al., 2012)
Human-trial status: one small study (33 older adults with type 2 diabetes against untreated controls; randomization and dose not reported in the abstract) found lower fasting glucose and insulin resistance (Korkushko et al., 2011); no randomized trial

References

Side effects

No controlled safety study has been published in any species, and the animal and cell studies, almost all from the developing institute, were not designed to detect harm. It lowered blood glucose in diabetic rats and in old monkeys, and its interaction with glucose-lowering drugs has not been studied (Goncharova 2014). Commonly reported (anecdotal): injection-site irritation with injectable forms; oral capsules draw few complaints.

Storage

Storage: Room temperature
Lyophilized: 24+ months

Pharmacology

Half-life: No published pharmacokinetic data in any species
Bioavailability: Not measured. Active orally in diabetic rats (Khavinson 2007)
Molecular weight: 575.61 Da
Sequence: KEDW[NH2] (Lys-Glu-Asp-Trp-NH2)