FOXO4-DRI vs PGPIPN
Side-by-side comparison of key properties, dosing, and research.
- Summary
- FOXO4-DRI is a D-retro-inverso peptide derived from the FOXO4 protein that selectively induces apoptosis in senescent cells. By disrupting the FOXO4-p53 interaction that keeps senescent cells alive, it triggers programmed cell death specifically in these aging, pro-inflammatory cells while sparing healthy tissue.
- PGPIPN is a bioactive hexapeptide (Pro-Gly-Pro-Ile-Pro-Asn) derived from beta-casein during enzymatic digestion. It exhibits anti-inflammatory properties via opioid receptor modulation and cytokine suppression, making it relevant for gut health, systemic inflammation, and as a component of casein-derived functional foods.
- Half-Life
- Estimated 2-4 hours (D-amino acid confers resistance to proteolysis)
- Estimated 30-120 minutes (peptide degradation)
- Admin Route
- Subcutaneous, Intraperitoneal (research)
- Oral, Subcutaneous (research)
- Research
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- Typical Dose
- 5 mg/kg in rodent studies; human equivalent approximately 0.5-1 mg/kg
- 200-500 mg per day
- Frequency
- 3 consecutive days per cycle
- Once or twice daily
- Key Benefits
- Selectively clears senescent cells (senolytics)
- Reduces senescence-associated secretory phenotype (SASP) and chronic inflammation
- Demonstrated restoration of physical fitness in aged mice
- May improve healthspan and reduce age-related tissue dysfunction
- Potential for treatment of age-related pathologies driven by cellular senescence
- Does not affect healthy non-senescent cells at therapeutic doses
- Anti-inflammatory effects via cytokine suppression
- Gut mucosal protection and intestinal barrier support
- Opioid receptor modulation for gut motility regulation
- Potential analgesic activity via central and peripheral opioid pathways
- Explored for inflammatory bowel conditions and gut dysbiosis
- Natural origin (food-derived) with favorable safety profile
- Side Effects
- Limited human data; largely preclinical evidence
- Possible temporary inflammatory response as senescent cells are cleared (senolytic effect)
- Weight loss observed at high doses in rodent studies
- Unknown long-term safety profile in humans
- Generally very well-tolerated given food-derived origin
- Theoretical opioid-mediated constipation at high doses
- Rare milk protein allergy in casein-sensitive individuals
- Stacks With
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