Chemistry:FOXO4-DRI

From HandWiki

FOXO4-DRI is a synthetic peptide derivative that is described as an all D-enantiomer retro-inverso peptide[1] It blocks the activity of Forkhead box protein O4 (FOXO4), a transcription factor which is elevated in senescent cells, and helps maintain their viability. Blocking FOXO4, which inhibits the activation of P53, causes senescent cells to undergo apoptosis by P53 activation, without affecting healthy cells around them, and has anti-aging effects which may have potential applications in the treatment of numerous age-related diseases, as well as an adjunct to treatment for certain forms of cancer.[2][3][4][5][6][7][8][9] It has the sequence H-ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg-OH.[10]

See also

  • Tertomotide

References

  1. ↑ "Recent Applications of Retro-Inverso Peptides". International Journal of Molecular Sciences 22 (16): 8677. August 2021. doi:10.3390/ijms22168677. PMID 34445382. 
  2. ↑ "Rejuvenation by Therapeutic Elimination of Senescent Cells". Cell 169 (1): 3–5. March 2017. doi:10.1016/j.cell.2017.03.014. PMID 28340347. 
  3. ↑ "Cellular senescence as a therapeutic target to improve renal transplantation outcome". Pharmacological Research 130: 322–330. April 2018. doi:10.1016/j.phrs.2018.02.015. PMID 29471104. 
  4. ↑ "FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice". Aging 12 (2): 1272–1284. January 2020. doi:10.18632/aging.102682. PMID 31959736. 
  5. ↑ "Targeting senescence-like fibroblasts radiosensitizes non-small cell lung cancer and reduces radiation-induced pulmonary fibrosis". JCI Insight 6 (23). December 2021. doi:10.1172/jci.insight.146334. PMID 34877934. 
  6. ↑ "FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice". Naunyn-Schmiedeberg's Archives of Pharmacology 396 (10): 2393–2403. October 2023. doi:10.1007/s00210-023-02452-2. PMID 37074394. 
  7. ↑ "FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells". Experimental Gerontology 195. October 2024. doi:10.1016/j.exger.2024.112522. PMID 39025385. 
  8. ↑ "FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation". Communications Biology 8 (1). February 2025. doi:10.1038/s42003-025-07738-0. PMID 39994346. 
  9. ↑ "The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI". Nature Communications 16 (1). July 2025. doi:10.1038/s41467-025-60844-9. PMID 40593617. Bibcode: 2025NatCo..16.5672B. 
  10. ↑ "Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging". Cell 169 (1): 132–147.e16. March 2017. doi:10.1016/j.cell.2017.02.031. PMID 28340339. 



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