FOXO4-DRI: A Laboratory Research Reference

FOXO4 (here referring to the FOXO4-DRI peptide described in the research literature) is a synthetic peptide designed to disrupt the interaction between the FOXO4 transcription factor and p53. It is studied in laboratory research for its effects on senescent cells in experimental models.

This page is a non-promotional scientific reference for researchers. It summarises the chemical identity, molecular characteristics, mechanism as described in the literature, research areas, and analytical testing of the FOXO4-DRI peptide. It does not provide dosing, therapeutic, or human-use guidance of any kind. FOXO4-DRI supplied by Bulk Aussie Peptides is for laboratory research purposes only.

What Is FOXO4-DRI?

FOXO4-DRI is a synthetic peptide antagonist engineered to compete with the FOXO4 transcription factor for binding to p53. It is a relatively long peptide reported to incorporate D-amino acid residues for stability, combined with a cell-penetrating component. The purpose of the design is to release p53 from FOXO4-mediated retention, which in senescent cells is reported to favour apoptosis.

For background on how synthetic research peptides are produced and verified, see the synthetic peptides research guide.

Molecular Characteristics

Several molecular properties are used to identify FOXO4-DRI in analytical documentation:

• Classification: a synthetic peptide antagonist of the FOXO4–p53 interaction, described as a senolytic research peptide.
• Composition: a long peptide incorporating D-amino acid residues and a cell-penetrating element; the exact sequence should be read from the specific study.
• Molecular weight: reported in Daltons (Da) on product documentation; the measured value on a Certificate of Analysis should be compared against the theoretical mass derived from the sequence.
• Physical form: supplied as a lyophilised (freeze-dried) powder, the standard presentation for research peptides.

How FOXO4-DRI Works

FOXO4-DRI is described as displacing FOXO4 from p53 in the nucleus, promoting the export of p53 to the mitochondria where it contributes to the induction of apoptosis in senescent cells. Structural studies have characterised the interaction of the disordered FOXO4-DRI peptide with the disordered transactivation domain of p53, providing a molecular description of the competition the peptide exploits.

These observations are preclinical and describe peptide–protein interactions in model systems; they do not constitute a therapeutic use.

Areas of Scientific Research

The research literature describes several lines of investigation involving FOXO4-DRI:

• Senescence biology: studies of selective removal of senescent cells in cultured-cell and tissue models.
• p53 signalling: characterisation of the FOXO4–p53 interaction and its structural basis.
• Peptide design: work developing modified FOXO4-DRI variants and alternative senolytic peptides.

These investigations are conducted in vitro or in approved animal research models under institutional oversight. They do not translate to approved human use.

Analytical Testing

As with other research peptides, FOXO4-DRI is characterised using:

• HPLC for purity assessment, reported as a percentage of total peak area.
• Mass spectrometry for identity confirmation, by comparing measured molecular mass to the theoretical value.

Guidance on interpreting the resulting documents is available in the article on how to read a peptide Certificate of Analysis.

Storage and Handling

In a laboratory context, lyophilised FOXO4-DRI is typically stored in a freezer, protected from light and moisture, and handled according to the product-specific documentation. Once reconstituted, the resulting solution is refrigerated and used within the timeframe stated in the documentation. General guidance is covered in the peptide storage and stability reference.

Frequently Asked Questions

• What is FOXO4-DRI? FOXO4-DRI is a synthetic peptide that disrupts the interaction between FOXO4 and p53.
• What is FOXO4-DRI studied for? It is investigated in laboratory models for effects on senescent cells and p53 signalling.
• What does DRI stand for? DRI stands for “D-retro-inverso”, referring to the use of D-amino acids in the peptide design.
• Is FOXO4-DRI a drug? No, it is a research peptide with no regulatory approval for therapeutic use.
• How is FOXO4-DRI purity tested? Purity is commonly estimated by HPLC, while identity is confirmed by mass spectrometry.

References

• Bourgeois, B., & Madl, T. (2018). Regulation of cellular senescence and p53 by FOXO4. Seminars in Cancer Biology. — Provides the structural and signalling context for the FOXO4–p53 interaction.
• Baar, M. P., Brandt, R. M. C., Putavet, D. A., et al. (2017). Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell, 169(1), 132–147. — Introduces the FOXO4-DRI senolytic peptide. See also the 2025 structural characterisation at PubMed 40593617.

Related Research Resources

• SS-31: A Laboratory Research Reference — a mitochondrial-targeting research peptide.
• Thymalin: A Laboratory Research Reference — a related bioregulator peptide.
• Synthetic Peptides: Research Guide — how research peptides are produced and verified.