
FOXO4
A retro-inverso peptide designed to disrupt the FOXO4-p53 interaction that keeps senescent cells viable.
- Purity
- 99.2%
- Lot
- PU-27C8
- Format
- Lyophilized powder
- Third-party tested
- Discreet packaging
- Same-day shipping
- Encrypted checkout
For research use only. Not for human consumption.
Mechanism of Action
FOXO4-DRI is a D-amino-acid retro-inverso peptide designed to interfere with the interaction between FOXO4 and the p53 transactivation domain. In senescent cells that interaction sequesters p53 in the nucleus; disrupting it has been reported to permit nuclear exclusion of p53 and apoptosis of the senescent cell, while non-senescent cells are less affected.
The structural basis has been examined in detail. Work in Protein Science, Nature Communications and the FEBS journals has characterised the FOXO4 DNA-binding domain and p53 transactivation-domain interaction, its structural plasticity, and how the peptide targets it.
Research Findings
The founding study was published in Cell in 2017, reporting targeted apoptosis of senescent cells and tissue-homeostasis endpoints in mouse models of chemotoxicity. Subsequent work applied the peptide to expanded human chondrocytes, endothelial senescence, keloid fibroblasts and aged rodent tissue.
The literature also contains an important counterweight: a 2023 report in Circulation described senescent-cell elimination promoting pulmonary hypertension in one model. Senolytic effects are not uniformly favourable across tissues, and the review literature regards this as unsettled.
Storage & Reconstitution
Sealed lyophilized vials are stored in the dark. The peptide-formulation literature regards the dry solid as the stable state and the solution as the fragile one: refrigeration at 2-8 degrees C is standard for short holding periods, and minus 20 degrees C or colder for long-term storage. Vials are brought to room temperature before opening so that atmospheric moisture does not condense onto the cold solid. Retro-inverso D-peptides are markedly more protease-resistant than their L-amino-acid counterparts, which is reflected in their handling literature.
For reconstitution, the diluent is added slowly down the inner wall of the vial rather than directly onto the cake, and the vial is swirled rather than shaken - agitation at an air-liquid interface is a well-documented driver of peptide aggregation. The solid should dissolve to a clear, particle-free solution; persistent cloudiness or visible particulate indicates the material should not be used.
Reconstituted solution is held at 2-8 degrees C and protected from light. Freeze-thaw cycling is the single most avoidable cause of loss, so where a solution must be frozen it is aliquoted first into single-use volumes. Working aliquots are labelled with the lot number so that any result can be traced back to the certificate of analysis for that lot.
- Physical form
- Lyophilized powder, sealed vial
- Sealed storage
- 2-8 C short term / -20 C long term
- Reconstituted
- 2-8 C, protected from light
- Diluent
- Bacteriostatic water, added down the vial wall
- Avoid
- Shaking, freeze-thaw cycling, direct light
Handling summary
References
Every entry below links to its PubMed record. Publication is not endorsement: several of these papers report limitations, negative findings or adverse events, and they are listed for that reason.
- [1]Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression(opens PubMed in a new tab)
Circulation · 2023 · PMID 36515093
- [2]
- [3]
- [4]The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI(opens PubMed in a new tab)
Nat Commun · 2025 · PMID 40593617
- [5]Peptide Inhibitors Targeting FOXO4-p53 Interactions and Inducing Senescent Cancer Cell-specific Apoptosis(opens PubMed in a new tab)
J Med Chem · 2025 · PMID 40739602
- [6]FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway(opens PubMed in a new tab)
Front Bioeng Biotechnol · 2025 · PMID 41625068