Foxo4 Dri: Chemical Properties
18 Citas PubMedRevisado por EspecialistasCertificado GMPÚltima Revisión: abril de 2026
Propiedades Químicas
| Molecular Formula | C₂₂₈H₃₈₈N₈₆O₆₄ |
| Molecular Weight | 5358.05 Da |
| CAS Number | 2460055-10-9 |
| PubChem CID | 167312269 |
| Sequence (1-Letter) | H-ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg-OH (all D-amino acids) |
| Sequence (3-Letter) | H-D-Leu-D-Thr-D-Leu-D-Arg-D-Lys-D-Glu-D-Pro-D-Ala-D-Ser-D-Glu-D-Ile-D-Ala-D-Gln-D-Ser-D-Ile-D-Leu-D-Glu-D-Ala-D-Tyr-D-Ser-D-Gln-D-Asn-D-Gly-D-Trp-D-Ala-D-Asn-D-Arg-D-Arg-D-Ser-D-Gly-D-Gly-D-Lys-D-Arg-D-Pro-D-Pro-D-Pro-D-Arg-D-Arg-D-Arg-D-Gln-D-Arg-D-Arg-D-Lys-D-Lys-D-Arg-D-Gly-OH |
| Structure | 46-amino acid D-retro-inverso peptide; all D-amino acids in reversed sequence; fused to HIV-TAT cell-penetrating domain (GRKKRRQRRR); derived from FOXO4 Forkhead domain (N-terminal disordered region + alpha-helix 1) |
| Origin | Designed by Peter L.J. de Keizer at Erasmus University Medical Center Rotterdam / Cleara Biotech B.V. |
| Classification | Senolytic Peptide / D-Retro-Inverso Peptide / Research Peptide |
| Half-Life | Short in vivo half-life (drives development of newer variants); intracellular detection up to 72 hours post-administration |
| Bioavailability | Cell-permeable via HIV-TAT domain; intracellular uptake within 2-4 hours |
Identificadores
| Purity Standard | ≥95–98% by HPLC |
| Synonyms | FOXO4-DRI, Proxofim, FOXO4 D-Retro-Inverso peptide, FOXO4 DRI |
| InChI Key | WVZCDZFJLXBWHG-XXZPGMBKSA-N |
| Developer | Cleara Biotech B.V. (Utrecht, Netherlands) |
Referencias
- Baar MP, et al. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell, 169(1), 132-147.e16, 2017.
- Bourgeois B, et al. The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI. Nature Communications, 16(1), 5672, 2025.
- Bourgeois B, Madl T. Regulation of cellular senescence via the FOXO4-p53 axis. FEBS Letters, 592(12), 2083-2097, 2018.
- Zhang C, et al. FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging, 12(2), 1272-1284, 2020.
- Hu Z, et al. FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway. Frontiers in Bioengineering and Biotechnology, 13, 1729166, 2026.
- Huang Y, et al. Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes. Frontiers in Bioengineering and Biotechnology, 9, 677576, 2021.
- Li Y, et al. FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells. Experimental Gerontology, 195, 112522, 2024.
- Han X, et al. FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway. Journal of Cellular and Molecular Medicine, 26(11), 3269-3280, 2022.
- Liu Y, et al. 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, 2023.
- Putavet DA, et al. Abstract IA002: Targeting senescence heterogeneity against cancer therapy-resistance and metastases. Cancer Research, 81(5_Supplement), IA002, 2021.
- Meng J, et al. Targeting senescence-like fibroblasts radiosensitizes non-small cell lung cancer and reduces radiation-induced pulmonary fibrosis. JCI Insight, 6(23), e146334, 2021.
- Krimpenfort P, Berns A. Rejuvenation by Therapeutic Elimination of Senescent Cells. Cell, 169(1), 3-5, 2017.
- Mandal R, et al. FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA. Protein Science, 31(5), e4287, 2022.
- Kong YX, et al. FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation. Communications Biology, 8(1), 299, 2025.
- van Willigenburg H, de Keizer PLJ, de Bruin RWF. Cellular senescence as a therapeutic target to improve renal transplantation outcome. Pharmacological Research, 130, 322-330, 2018.
- Putavet D, et al. Abstract P1-19-02: Repurposing the FOXO4 senolytic against triple-negative breast cancer. Cancer Research, 82(4_Supplement), P1-19-02, 2022.
- Nwankwo N, Okafor I. Bioinformatics procedure for investigating senolytic (anti-aging) agents: A digital signal processing technique. Aging Medicine, 6(4), 338-346, 2024.
- Timucin E, et al. Novel Senolytic Peptides. United States Patent Application, US20200255489A1, 2020.
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