FOXO4-DRI

A synthetic D-retro-inverso peptide studied as a tool to disrupt the FOXO4–p53 protein–protein interaction in cellular-senescence research.

Molecular Profile

Type
Synthetic D-retro-inverso peptide (45 residues)
Molecular formula
C228H388N86O64
Molecular weight
5358.05 g/mol
CAS number
2460055-10-9
Amino acids
45
Sequence
LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRPPPRRRQRRKKRG (D-retro-inverso isoform)
Modification
All-D-amino-acid retro-inverso isoform (reversed sequence of the FOXO4 p53-interacting segment); free N- and C-termini.

Mechanism & Target Class

FOXO4-DRI corresponds to the reversed, all-D-amino-acid version of the FOXO4 segment that engages the tumor-suppressor protein p53; it carries an arginine-rich cell-penetrating segment at its C-terminus. The research literature characterizes it as a competitive disruptor of the FOXO4–p53 protein–protein interaction. In the originating model (Baar et al., 2017), FOXO4 is described as sequestering p53 in nuclear PML bodies in senescent cells; the peptide is studied for its capacity to interfere with that interaction, and assays measure p53 nuclear localization and apoptosis endpoints in senescent versus non-senescent cell cultures. Subsequent solution-NMR and biophysical work has mapped the binding interface to the disordered p53 transactivation domain and the FOXO4 forkhead domain (Bourgeois et al., 2025; Kohoutova et al., 2025).

Storage & Handling

Lyophilized
−20°C desiccated and protected from light; −80°C for long-term storage.
Handling
Large arginine-rich peptide; protect from light and moisture and avoid freeze-thaw cycles.

Primary Database

PubChem CID 167312269 ↗

References (15)

  1. Reviews

    1

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    DOI: 10.1038/s41591-022-01923-yPubMed 35953721

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    Gorgoulis V, et al. (2019). Cell

    DOI: 10.1016/j.cell.2019.10.005PubMed 31675495

  3. 3

    Bourgeois B, Madl T. (2018). FEBS Lett

    DOI: 10.1002/1873-3468.13057PubMed 29683489

  4. Primary research

    4

    Huang H, et al. (2026). Front Bioeng Biotechnol

    DOI: 10.3389/fbioe.2025.1729166PubMed 41625068

  5. 5

    Bourgeois B, et al. (2025). Nat Commun

    DOI: 10.1038/s41467-025-60844-9PubMed 40593617

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    Kohoutova K, et al. (2025). Nat Commun

    DOI: 10.1038/s41467-025-59106-5PubMed 40425537

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    Kong X, et al. (2025). Commun Biol

    DOI: 10.1038/s42003-025-07738-0PubMed 39994346

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    Kang H, et al. (2024). Commun Biol

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    Kim J, et al. (2022). FEBS J

    DOI: 10.1111/febs.16333PubMed 34954873

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    Mandal R, et al. (2022). Protein Sci

    DOI: 10.1002/pro.4287PubMed 35481640

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    Huang Y, et al. (2021). Front Bioeng Biotechnol

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    Zhang C, et al. (2020). Aging (Albany NY)

    DOI: 10.18632/aging.102682PubMed 31959736

  15. 15

    Baar MP, et al. (2017). Cell

    DOI: 10.1016/j.cell.2017.02.031PubMed 28340339