FOXO4-DRI

FOXO4-DRI (also known as FOXO4-D-Retro-Inverso or Proxofim) is a synthetic, cell-penetrating peptide designed as a senolytic agent. It targets senescent cells (often called "zombie cells"), which accumulate with age, contribute to inflammation via the senescence-associated secretory phenotype (SASP), and drive various age-related conditions.

Mechanism of Action FOX04-DRI is a modified version of a segment from the FOX04 protein (a forehead box O transcription factor). It uses D-amino acids in a retro-inverse configuration for enhanced stability and resistance to degradation. In senescent cells, FOX04 binds to p53 (a key tumour suppressor protein), retaining p53 in the nucleus and preventing it from triggering apoptosis (programmed cell death). By competitively disrupting this FOX04-p53 interaction, FOX04-DRI allows p53 to be excluded from the nucleus (often relocating to mitochondria), activating caspase-dependent apoptosis specifically in senescent cells—while largely sparing healthy ones. This selective clearance of senescent cells has shown promise in restoring tissue function in preclinical models.

Key Research Findings Preclinical studies (primarily in cell cultures and mouse models) demonstrate that FOX04-DRI:

• Clears senescent fibroblasts, chondrocytes, Leydig cells, endothelial cells and other. 

§  Improves age-related issues.

§  Restoring kidney function in aged or fast-aging mice.

§  Alleviating testosterone insufficiency by targeting senescent Leydig cells.

§  Reducing chemotherapy-induced tissue damage.

§  Enhancing cartilage quality in expanded chondrocytes (by lowering SASP factors,

   though not always improving chondrogenesis).

§  Potentially aiding conditions like keloids, radiation-induced fibrosis, and vascular aging.

~ Mechanism of Action

• FOX04-DRI works by interfering with a specific protein interaction within senescent cells.

§ Normal Cells: In healthy, non-senescent cells, the protein FOX04 helps regulate cellular processes. In senescent cells, however, FOX04 binds to the tumour suppressor protein p53 within the nucleus, which prevents p53 from triggering cell death (apoptosis). This interaction allows the damaged, senescent cell to persist.

§  FOX04-DRI Action: The FOX04-DRI peptide is an all D-enantiomer retro-inverse peptide, meaning its structure is modified to be more resistant to degradation in the body. It enters senescent cells and competes with the endogenous FOX04 to bind with p53. This disruption causes the p53 protein to move out of the nucleus and to the mitochondria, where it then initiates the normal apoptotic pathway, resulting in the selective self-destruction and clearance of the senescent cell. 

• Product Details:

§  Name: FOX04-DRI.

§  Catalogue Number: 328-56.

§  Molecular Formula: C228H388N86O64.

§  Concentration: Lyophilised powder in 10ml vial.

§  Physical Form: Powder Form.

§  Purity Level: ≥99%

• Handling and Storage:

§  General Dosage: FOX04 - Typical Dose: 1-5mg every 3 days. Cycle length: 1-2 weeks.

§  Storage: Store this product in a dry place, away from sunlight and moisture.

      Storage temperature should not exceed 25°C.

§  Reconstitute: Reconstitute with Bacteriostatic Water. Swirl gently do not vortex.

§  After Reconstitute: Store at 2-8 °C. To minimise freeze thaw, prepare aliquots according to your protocol.

§  Compatibility: Use only within research protocols that follow your lab's SOPs and local regulations.

For Research Use Only

This product is supplied strictly for scientific research and laboratory experimentation. It is not intended for human consumption, clinical use or any form of therapeutic application.