FOX04-DRI
Forkhead Box Protein O4 D-Retro-Inverso Peptide
FOXO4-DRI (Forkhead Box O4 D-Retro-Inverso) is a cell-penetrating, synthetic peptide designed to counter the effects of cellular senescence. In non-senescent cells, p53 regulates DNA repair and apoptosis, but in senescent states, it is sequestered by the transcription factor FOXO4, locking cells in a state of permanent growth arrest while sustaining the secretion of pro-inflammatory factors known as the senescence-associated secretory phenotype (SASP). By utilizing a D-retro-inverso configuration, FOXO4-DRI mirrors the spatial topology of the natural FOXO4 interaction domain while exhibiting enhanced resistance to endogenous proteolytic degradation. Preclinical investigations focus on its ability to selectively target senescent cell populations across diverse tissue models without compromising non-senescent cell viability.
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- Purity
- ≥99%
- Form
- Lyophilized powder
- CAS Number
- 2170817-48-2
- Molecular Formula
- C228H388N86O64
- Molecular Weight
- 5358.1 g/mol
- Available sizes
- 10mg
Sequence
H-dLeu-dThr-dLeu-dArg-dLys-dGlu-dPro-dAla-dSer-dGlu-dIle-dAla-dGln-dSer-dIle-dLeu-dGlu-dAla-dTyr-dSer-dGln-dAsn-dGly-dTrp-dAla-dAsn-dArg-dArg-dSer-dGly-dGly-dLys-dArg-dPro-dPro-dPro-dArg-dArg-dArg-dGln-dArg-dArg-dArg-NH2
Mechanism of Action
FOXO4-DRI acts as a competitive antagonist against the endogenous binding interaction between FOXO4 and the tumor suppressor p53. In senescent cells, FOXO4 binds p53 within the nucleus, preventing it from executing apoptosis. FOXO4-DRI competitively binds to the complex, dislodging p53 and facilitating its translocation from the nucleus to the cytoplasm and mitochondria. Once released, p53 triggers mitochondrial outer membrane permeabilization, which leads to the activation of the intrinsic apoptotic cascade via caspase-3 and caspase-9 cleavage. Because non-senescent cells rely on alternative survival and regulatory pathways that do not hyper-depend on FOXO4-p53 sequestration, FOXO4-DRI-mediated apoptotic signaling remains selective to senescent phenotypes in laboratory models.
Research Areas
- ●Cellular Senescence and Senolytics
- ●Longevity and Lifespan Extension Models
- ●Tissue Fibrosis and Regeneration
- ●Cardiovascular and Metabolic Aging
- ●SASP Modulation and Inflammaging
Selected References
- Baar MP, et al. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell. 2017.
- de Keizer PLJ. The Fountain of Youth by Targeting Senescent Cells? Trends Mol Med. 2017.
- Zhang C, et al. FOXO4-DRI peptide induces apoptosis of senescent chondrocytes in osteoarthritis models. Aging Cell. 2020.
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