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Longevity & Cellular Health Preclinical / Research Only PubChem CID: 139591410

FOXO4-DRI: Clinical Mechanism, Dossier & Protocols

D-retro-inverso peptide that disrupts the FOXO4-p53 interaction specifically in senescent "zombie" cells, triggering targeted apoptosis of senescent cells while leaving healthy cells completely unharmed.

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🔬 Molecular Architecture & Physical Specifications

Molecular Weight
5358.1 g/mol
Chemical Formula
C232H382N72O54
Elimination Half-Life
Extended stability due to all D-amino acid backbone resistance to proteases
Administration Route
Subcutaneous (SC), Intraperitoneal / IV (Research)
NCBI PubChem Record
Amino Acid Sequence: D-Retro-Inverso peptide composed of 44 D-amino acids derived from FOXO4 and p53 binding domains

⚙️ Primary Mechanism of Action

Selectively interferes with the FOXO4-p53 complex in senescent cells; causes p53 to translocate to the mitochondria, inducing apoptosis specifically in senescent cells and eliminating the harmful SASP secretory profile.

💉 Research Dosage & Reconstitution Standard

Requires pharmaceutical-grade 0.9% benzyl alcohol Bacteriostatic Water to inhibit bacterial replication for multi-dose access.

Full Step-by-Step Guide →
Standard Vial Sizes
5mg, 10mg
Target Research Dose
1mg to 3mg every 2 - 3 days for 3 doses (Pulse Senolytic Protocol)
Administration Frequency
Pulsed dosing 2-3 times per week for 1-2 weeks only
💧 Dilution Standard: Reconstitute with sterile Bacteriostatic Water for Injection (USP). Aim stream gently along the vial glass wall to avoid foaming. Store reconstituted solution at 2°C to 8°C (36°F to 46°F) protected from light. Discard multi-dose punctured vials at 28 days pursuant to USP <797> standards. Never freeze reconstituted liquid.

⚠️ Contraindications & Documented Adverse Effects

Strict Contraindications

  • Active infection or acute injury recovery phase (where temporary senescence is required for healing)

Documented Side Effects

  • Fatigue during the 48-72h senescent clearance window
  • Mild immune activation symptoms
  • Injection site tenderness

📚 Peer-Reviewed References & Authoritative Sources

Citations indexed in PubMed, National Center for Biotechnology Information (NCBI), and ClinicalTrials.gov.

1 VERIFIED CITATIONS
Cell (2017; 169:132-147)
Pioneering investigation demonstrating FOXO4-DRI disrupts senescent cell survival mechanisms, clearing senescent cells and restoring renal function.
PMID: 28343997 · DOI: 10.1016/j.cell.2017.02.031

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