1. Identity
| Property | Detail |
|---|---|
| Name | FOXO4-DRI (FOXO4 D-retro-inverso) |
| Composition | D-amino-acid, reversed-order sequence derived from the p53-binding region of FOXO4, linked to a cell-penetrating HIV-TAT segment |
| Approx. molecular weight | ≈5,358 Da |
| Molecular target | The FOXO4–p53 protein interaction |
2. The D-retro-inverso principle
A retro-inverso sequence is built from D-amino acids assembled in the reverse order of the parent L-sequence. The side chains end up in nearly the same spatial positions as in the original, so the molecule can mimic the parent surface, while the D-configured backbone is not recognized by most proteases. FOXO4-DRI applies this principle to the region of FOXO4 that contacts p53.
3. The FOXO4–p53 interaction
FOXO4 is a forkhead-box transcription factor; p53 is a transcription factor that controls cell-division arrest and apoptosis programs. Structural and biophysical studies (Mandal et al. 2022; Kim et al. 2022; Kohoutova et al. 2025) show that FOXO4 engages p53 through more than one surface, including the disordered p53 transactivation domain (TAD). Bourgeois and colleagues (2025) reported that this transactivation domain is also the site targeted by FOXO4-DRI.
4. The senolytic concept
Senescent cells are cells that have permanently stopped dividing but remain viable. The term “senolytic” describes compounds that selectively trigger apoptosis in such cells. FOXO4-DRI was introduced by Baar and colleagues in 2017 on the hypothesis that FOXO4 holds p53 in the nucleus of senescent cells, and that releasing p53 would push those cells toward apoptosis. Tripathi and colleagues (2021) later developed a novel compound by more precisely disrupting the FOXO4–p53 complex.
5. Analytical characterization
Identity and purity are confirmed analytically for every lot. Reversed-phase HPLC with UV detection quantifies chromatographic purity, and electrospray mass spectrometry (ESI-MS) confirms that the observed molecular mass matches the theoretical value for FOXO4-DRI.
Results are reported on a lot-specific certificate of analysis together with appearance, net content and the lot number, which allows any vial to be traced back to its analytical record.
6. Storage and handling
Material is supplied as a lyophilized solid in a sealed vial. Unopened vials are best kept at −20 °C, protected from light and moisture. Allow a vial to equilibrate to room temperature before opening to limit condensation, and record the lot number so the vial can be matched to its certificate of analysis.
A lot-specific certificate of analysis is available for each batch.
Sources
- Bourgeois B, Madl T. Regulation of cellular senescence via the FOXO4-p53 axis. FEBS Lett. 2018. doi:10.1002/1873-3468.13057. PMID: 29683489. PubMed.
- Mandal R, Kohoutova K, Petrvalska O, et al. FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA. Protein Sci. 2022. doi:10.1002/pro.4287. PMID: 35481640. PubMed.
- Kim J, Ahn D, Park CJ, et al. Biophysical investigation of the dual binding surfaces of human transcription factors FOXO4 and p53. FEBS J. 2022. doi:10.1111/febs.16333. PMID: 34954873. PubMed.
- Bourgeois B, Spreitzer E, Platero-Rochart D, et al. The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI. Nat Commun. 2025. doi:10.1038/s41467-025-60844-9. PMID: 40593617. PubMed.
- Kohoutova K, Srb P, Obsilova V, et al. Structural plasticity of the FOXO-DBD:p53-TAD interaction. Nat Commun. 2025. doi:10.1038/s41467-025-59106-5. PMID: 40425537. PubMed.
- Tripathi U, Chaib S, Gerdes EOW, et al. Development of a novel senolytic by precise disruption of FOXO4-p53 complex. EBioMedicine. 2021. doi:10.1016/j.ebiom.2021.103693. PMID: 34768086. PubMed.
Research Use Only. All products sold by ShortChain Aminos are intended strictly for laboratory research purposes. They are not for human or veterinary use, and nothing in this article constitutes medical advice, usage instructions, or a recommendation of any kind. This content summarizes published third-party research for informational purposes only.