PGPIPN
A milk-derived hexapeptide from bovine beta-casein with immunomodulatory, anticancer, and hepatoprotective properties studied primarily in ovarian cancer and liver disease models.
What is PGPIPN?
PGPIPN (Pro-Gly-Pro-Ile-Pro-Asn) is a six-amino-acid peptide corresponding to residues 63-68 of bovine beta-casein. It is naturally encrypted within milk protein and released during enzymatic digestion. Its three proline residues make it unusually resistant to further degradation by digestive enzymes, allowing it to survive the gastrointestinal tract and reach systemic circulation when taken orally. Originally identified for its immunomodulatory properties — enhancing macrophage phagocytosis and lymphocyte proliferation — it has since been studied for anticancer effects (particularly against ovarian cancer) and for protecting the liver from alcohol-induced damage.
Why People Talk About It
Ovarian cancer growth suppression (BCL2-mediated apoptosis)
PreliminaryOvercoming cisplatin resistance in ovarian cancer (HSF1/HSP70 pathway)
PreliminaryImmune enhancement (macrophage phagocytosis, lymphocyte proliferation)
PreliminaryAlcoholic liver disease protection (fatty liver and acute injury)
PreliminaryAnti-invasion and anti-metastasis properties (MTA1/NM23H1 regulation)
PreliminaryHow It Works
PGPIPN is a tiny, digestion-resistant peptide from milk protein that works through multiple pathways. In cancer cells, it triggers programmed cell death by suppressing the survival protein BCL2 and can help overcome chemotherapy resistance. In the immune system, it boosts the activity of macrophages (immune cells that engulf pathogens) and promotes lymphocyte proliferation. In the liver, it reduces inflammation, oxidative stress, and the ER stress response that drives alcohol-related damage.
Common Questions
Safety Information
Common Side Effects
Cautions
- • Not FDA-approved for any indication
- • No human clinical trials have been conducted
- • All data comes from cell culture and animal models
- • Optimal human dosing is completely unknown
What We Don't Know
Human safety, pharmacokinetics, and efficacy are entirely unestablished. All research to date has been preclinical (in vitro and animal studies), primarily from a single research group at Anhui Medical University in China. No human clinical trials have been published.
Published Research
7 studiesBioactive hexapeptide reduced the resistance of ovarian cancer cells to DDP by affecting HSF1/HSP70 signaling pathway
PGPIPN synergistically enhances cisplatin sensitivity by reducing HSF1/HSP70, MDR1, and ERCC1 in resistant ovarian cancer cells.
Milk-derived hexapeptide PGPIPN prevents and attenuates acute alcoholic liver injury in mice by reducing endoplasmic reticulum stress
PGPIPN attenuated acute alcoholic liver injury through PERK/eIF-2alpha ER stress pathway inhibition and anti-inflammatory effects.
Therapeutic hexapeptide (PGPIPN) prevents and cures alcoholic fatty liver disease by affecting the expressions of genes related with lipid metabolism and oxidative stress
PGPIPN prevented and treated alcohol-induced fatty liver in mice via ACC/PPAR-gamma modulation and oxidative stress reduction.
Construction of an anticancer fusion peptide (ACFP) derived from milk proteins and an assay of anti-ovarian cancer cells in vitro
Designed ACFP fusion peptide from PGPIPN and lactoferricin; demonstrated superior anti-ovarian cancer activity over individual peptides.
The milk-derived fusion peptide ACFP suppresses the growth of primary human ovarian cancer cells by regulating apoptotic gene expression and signaling pathways
Fusion peptide combining PGPIPN with lactoferricin showed enhanced anticancer activity against primary ovarian cancer cells.
The milk-derived hexapeptide PGPIPN inhibits the invasion and migration of human ovarian cancer cells by regulating the expression of MTA1 and NM23H1 genes
Showed PGPIPN inhibits ovarian cancer invasion/migration via MTA1 repression and NM23H1 upregulation in SKOV3 and primary tumor cells.
PGPIPN, a therapeutic hexapeptide, suppressed human ovarian cancer growth by targeting BCL2
Demonstrated PGPIPN inhibits SKOV3 proliferation and induces apoptosis via BCL2 downregulation; 68% tumor reduction in xenograft mice.
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Quick Facts
- Class
- Milk-Derived Bioactive Hexapeptide
- Evidence
- Preliminary
- Safety
- Limited Data
- Updated
- Apr 2026
- Citations
- 7PubMed
Also known as
Tags
Related Goals
Evidence Score
Clinical Trials
View Clinical TrialsLinks to ClinicalTrials.gov for reference. Listing does not imply endorsement.