FOXO4-DRI - 10MG

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FOXO4-DRI - 10MG
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Product Overview

FOXO4-DRI Senolytic Profile

FOXO4-DRI is a D-retro-inverso peptide that selectively induces apoptosis in senescent cells by disrupting the FOXO4–p53 interaction, a key survival axis for cellular senescence.[1]

Mechanism of Action

  • Binds the disordered p53 transactivation domain (TAD2), forming a transient complex that prevents FOXO4 from sequestering p53 in the nucleus.[1]
  • Drives nuclear exclusion of p53 in senescent cells → apoptosis; affinity is enhanced when p53 is phosphorylated (common in senescence/stress).[1]

Preclinical Efficacy

  • Pulmonary fibrosis (bleomycin models): ↓ senescent burden and SASP, ↓ collagen deposition/ECM production, improved lung structure and function; effects comparable to pirfenidone; downregulates ECM–receptor interaction pathway and reduces myofibroblasts while increasing type 2 alveolar epithelial cells/fibroblasts.[2,3]
  • Age-related hypogonadism: Eliminates senescent Leydig cells, restores testicular milieu, and improves testosterone synthesis in naturally aged mice.[4]

Therapeutic Landscape & Rationale

  • FOXO family (incl. FOXO4) orchestrates stress resistance, tumor suppression, and longevity; targeting FOXO protein–protein interactions is a promising strategy in aging, cancer, and fibrosis.[5–12]
  • Translational status: No human clinical data yet; optimal dosing, safety, and long-term outcomes remain to be established.

Key Takeaways

  • Mechanistically precise senolytic: Disrupts FOXO4–p53 to trigger senescent-cell apoptosis.
  • Disease modification signals: Benefits in lung fibrosis models and age-related testosterone insufficiency.
  • Needs clinical validation: Human dosing and safety profiles are currently undefined.

References

  1. Bourgeois B, Spreitzer E, Platero-Rochart D, et al. Nat Commun. 2025;16:5672. doi:10.1038/s41467-025-60844-9.[1]
  2. Han X, Yuan T, Zhang J, et al. J Cell Mol Med. 2022;26(11):3269-3280. doi:10.1111/jcmm.17333.[2]
  3. Liu Y, Hou Q, Wang R, et al. Naunyn-Schmiedeberg’s Arch Pharmacol. 2023;396(10):2393-2403. doi:10.1007/s00210-023-02452-2.[3]
  4. Zhang C, Xie Y, Chen H, et al. Aging. 2020;12(2):1272-1284. doi:10.18632/aging.102682.[4]
  5. Orea-Soufi A, Paik J, Bragança J, et al. Trends Pharmacol Sci. 2022;43(12):1070-1084.[5]
  6. Liu W, Li Y, Luo B. Cell Mol Life Sci. 2020;77(4):651-663.[6]
  7. Calissi G, Lam EW, Link W. Nat Rev Drug Discov. 2021;20(1):21-38.[7]
  8. Link W. Methods Mol Biol. 2019;1890:1-9.[8]
  9. Link W, Ferreira BI. Methods Mol Biol. 2025;2871:1-8.[9]
  10. Maiese K, Chong ZZ, Shang YC. Trends Mol Med. 2008;14(5):219-227.[10]
  11. Farhan M, Wang H, Gaur U, et al. Int J Biol Sci. 2017;13(7):815-827.[11]
  12. Maiese K, Chong ZZ, Shang YC, Hou J. Med Res Rev. 2009;29(3):395-418.[12]

All information provided is for research purposes only.

ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY. The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body. These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law.