FOXO4-DRI (Proxofim)

Description

Senolytic peptide for selective senescent cell clearance research.

FOXO4-DRI (Proxofim) is a D-retro-inverso peptide designed to disrupt the interaction between FOXO4 (Forkhead box O4) and p53 in senescent cells. In cellular senescence, FOXO4 sequesters p53 in the nucleus, preventing p53-mediated apoptosis and allowing damaged senescent cells to persist. FOXO4-DRI competitively binds FOXO4, displacing p53, which then translocates to mitochondria and triggers the intrinsic apoptotic pathway selectively in senescent cells, while leaving healthy cells unaffected due to their low FOXO4 expression. The landmark study by Baar et al. (2017) published in Cell demonstrated that FOXO4-DRI selectively induced apoptosis in senescent human fibroblasts in vitro and cleared senescent cells in naturally aged and fast-aging XpdTTD/TTD mice in vivo. Treated mice showed restored fur density, improved renal function, and increased exploratory behavior. This study established FOXO4-DRI as one of the first peptide-based senolytics with demonstrated in vivo efficacy. Follow-up research has explored its effects on senescence-associated secretory phenotype (SASP) reduction and tissue rejuvenation markers. Compared to small-molecule senolytics like dasatinib plus quercetin (D+Q) or navitoclax (ABT-263), FOXO4-DRI operates through a fundamentally different mechanism targeting the FOXO4-p53 protein-protein interaction rather than Bcl-2 family anti-apoptotic proteins or tyrosine kinases. The D-retro-inverso design provides protease resistance while maintaining binding specificity, though at a higher molecular weight than small-molecule alternatives. FOXO4-DRI must be stored lyophilized at -20°C and protected from light and moisture. Reconstitute with bacteriostatic water and store at 2-8°C, using within 2-3 weeks. This peptide is studied by aging biologists, senescence researchers, geroscientists, and nephrology and dermatology researchers investigating senolytic interventions for age-related tissue deterioration.

This product is supplied as a lyophilized powder and is intended for laboratory and research use only. Not for human consumption. Each vial contains 10mg of research-grade material.

Research Applications

• Senescent cell clearance studies
• Cardiovascular and renal function
• Insulin signaling and stress resilience
• Neurological health research

Specifications

Size

10mg

Purity

≥98% (HPLC)

Form

Lyophilized Powder

Molecular Formula

C228H388N86O64

Molecular Weight

5358.05 g/mol

Storage & Handling

• Long-term storage: -20°C in a sealed, light-protected container
• Short-term storage: 2-8°C (refrigerated) for up to 30 days
• Reconstituted: Store at 2-8°C and use within 30 days
• Avoid: Repeated freeze-thaw cycles, direct sunlight, and moisture exposure
• Reconstitution: Use bacteriostatic water or sterile water for injection