FOXO4-DRI (FOX04-DRI) — Peptyd Badawczy o Właściwościach Senolitycznych
✅ Synthetic ~28-aa D-amino-acid retro-inverso senolytic peptide
✅ Disrupts FOXO4-p53 binding → p53 mitochondrial translocation → senescent-cell apoptosis
✅ Landmark Baar/de Keizer/Demaria 2017 Cell-paper compound
✅ Selective senolysis: spares non-senescent cells; protease-resistant via D-AA design
✅ MW ~3,000 Da; canonical peptide senolytic research tool
FOXO4-DRI (also FOX04-DRI) contains synthetic retro-inverso senolytic research peptide.
✓ Zweryfikowany medycznie przez Morgan Ellis — Badacz farmaceutyczny · 8 lat doświadczenia · Ostatnia weryfikacja: maj 2026
Quick Answer — What is FOXO4-DRI?
FOXO4-DRI (also written FOX04-DRI; “DRI” = D-Retro-Inverso) is a synthetic ~28-amino-acid senolytic peptide developed by Baar, Brandt, de Keizer, Demaria, Campisi and colleagues at the Erasmus University Medical Center, and published in the landmark Cell paper “Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging” (Baar et al., March 2017). The peptide is the D-amino-acid retro-inverso version of a FOXO4 transactivation-domain fragment (corresponding to residues ~86–100 of human FOXO4). Sequence in conventional reading order: LTLRKEPASEIAQSILEAYSQNGWANRRSAGGNTPS (all D-amino acids, retro-inverso orientation; MW ~3,000 Da). Mechanism: FOXO4 normally tethers p53 to the nucleus of senescent cells, allowing them to evade apoptosis despite active p53 signalling. FOXO4-DRI competitively binds p53’s transactivation domain, displaces native FOXO4, and frees p53 to translocate to mitochondria — triggering selective senolysis (apoptosis of senescent cells only). Landmark “exercise-of-senescence” research compound. For laboratory research use only.
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| Specyfikacja | Szczegóły |
|---|---|
| Klasa związku | Synthetic ~28-aa D-amino-acid retro-inverso peptide; senolytic compound; p53-FOXO4 protein-protein interaction inhibitor |
| Nazwa chemiczna | FOXO4-DRI (alternative spellings: FOX04-DRI; FOXO4-D-Retro-Inverso; Baar/Demaria/de Keizer senolytic peptide; ProxoFen — earlier preclinical name) |
| Numer CAS | Research-grade peptide — no widely-registered single CAS; identification by published sequence (Baar et al. 2017) and supplier COA |
| Sequence (forward reading) | LTLRKEPASEIAQSILEAYSQNGWANRRSAGGNTPS (forward reading order; all 28 residues in Stereochemia D-aminokwasów, retro-inverso orientation relative to native L-FOXO4 sequence). Some published variants use a slightly different fragment length / residue range; consult COA for batch-specific sequence. |
| Masa cząsteczkowa | ~3,000 Da (varies slightly by published sequence variant) |
| Wzór cząsteczkowy | D-retro-inverso peptide — sequence-derived approximate MF C105H184N30O27; published MW ~2,330 Da. Exact formula varies slightly across supplier batches because the canonical Baar 2017 sequence has been replicated by multiple groups with minor cell-penetrating-peptide linker variants. |
| Mechanizm | In senescent cells, native FOXO4 binds the p53 transactivation domain and tethers p53 in the nucleus — preventing p53 from triggering apoptosis despite the cellular damage that activated p53 in the first place. This is part of why senescent cells survive and accumulate with ageing. FOXO4-DRI mimics the FOXO4-binding interface to p53 but in inverse-stereochemistry retro-inverso orientation — it competitively occupies the p53 binding site, displaces native FOXO4, and frees p53. The released p53 translocates to mitochondria where it triggers intrinsic apoptosis via the p53-mediated Bax / Bak / cytochrome-c-release cascade. Selective for senescent cells because they have both (a) FOXO4-tethered p53 and (b) activated p53 already; non-senescent cells have neither and are unaffected. |
| Domena proapoptotyczna KLAKLAKKLAKLAK jest syntetyzowana wyłącznie w | The retro-inverso D-amino-acid design confers protease-resistance — host proteases recognise only L-amino acids — extending in-vivo half-life and enabling oral / IP dosing in published rodent protocols. |
| Published In-Vivo Effects (Baar 2017) | Selective clearance of senescent cells from aged mice; restoration of fur density and quality; restoration of physical fitness / running endurance; restoration of renal function biomarkers; improvement in DOX-induced senescence-mediated injury models. The paper produced one of the most-cited demonstrations that senescent-cell clearance can functionally rejuvenate aged organisms. |
| Form / Purity / Storage | Lyophilized white-to-off-white powder, ≥99% HPLC. Store 2–8 °C short-term, −20 °C long-term. Reconstituted: 2–8 °C, use within 30 days. Avoid freeze-thaw. |
| Do celów badawczych | For laboratory research use only. Not on the WADA Prohibited List. Preclinical research compound. No formal human clinical trials of FOXO4-DRI itself; related senolytic compounds (dasatinib + quercetin, fisetin, navitoclax) are in clinical-translational research separately. |
Mechanism of Action — Selective Senolysis via p53-FOXO4 Disruption
FOXO4-DRI is the canonical research-tool example of peptide-based senolytic pharmacology. The senolytic concept (selectively killing senescent cells without affecting normal cells) is one of the most-cited current frameworks for anti-ageing therapeutics. FOXO4-DRI’s mechanistic story is unusually clean:
- Senescent cells accumulate with ageing — Tissue damage, DNA damage, oxidative stress, and other stressors trigger cells to enter the senescence state (irreversible cell-cycle arrest with persistent SASP — senescence-associated secretory phenotype). Senescent cells accumulate with ageing and contribute to age-related tissue dysfunction. Selective clearance of senescent cells reverses many age-related phenotypes in mouse models.
- FOXO4 tethers p53 in senescent cells — Senescent cells have elevated p53 levels and active p53 signalling. Normally, p53 would trigger apoptosis. But in senescent cells, the FOXO4 transcription factor binds p53 in the nucleus, tethering it there and preventing its translocation to mitochondria where it would otherwise initiate the intrinsic apoptosis cascade. This FOXO4-p53 tethering is part of the survival mechanism that allows senescent cells to persist.
- FOXO4-DRI as a peptidomimetic competitor — The peptide is designed to mimic the FOXO4-binding interface to p53 but in retro-inverse D-amino-acid orientation. It binds p53 with comparable affinity to native FOXO4 — competing for the same binding site. Treatment with FOXO4-DRI competitively displaces native FOXO4 from p53 in senescent cells.
- Released p53 → mitochondrial apoptosis — The freed p53 is no longer tethered to the nucleus and translocates to mitochondria. There it engages the canonical p53-mediated mitochondrial apoptosis cascade (Bax/Bak activation, cytochrome-c release, APAF-1 / caspase-9 / caspase-3 activation). The cell undergoes apoptosis.
- Selectivity for senescent cells — Non-senescent cells either don’t have activated p53 (so no apoptosis trigger), don’t have FOXO4-tethering (so FOXO4-DRI displacement has nothing to displace), or have both features at much lower levels. FOXO4-DRI is therefore highly selective for senescent cells in mouse studies.
- D-amino-acid protease resistance — The retro-inverso D-amino-acid design protects the peptide from proteolytic degradation, extending in-vivo half-life and allowing IP / oral dosing protocols.
Opublikowane zastosowania badawcze
- Senolytic pharmacology — canonical peptide example — most-cited peptide-based senolytic in published literature
- Ageing biology research — selective senescent-cell clearance from aged-mouse models
- p53-FOXO4 protein-protein-interaction pharmacology — useful reference compound for the broader p53-tethering biology
- Chemotherapy-induced senescence (TIS) research — DOX-induced senescence models, post-chemotherapy senescent-cell clearance
- Tissue-rejuvenation research — restoration of fur density, running endurance, renal function in aged mice (Baar 2017 readouts)
- Comparative senolytic research — vs small-molecule senolytics (dasatinib + quercetin, fisetin, navitoclax, ABT-263)
- D-amino-acid retro-inverso peptide design — exemplar of the protease-resistance design strategy
For broader context see Epitalon (Khavinson pineal-axis tetrapeptide — longevity research), SS-31 (Elamipretide) (mitochondrial-targeted antioxidant), MOTS-c (mitochondrial peptide), 5-Amino-1MQ (NAD-axis NNMT inhibitor). Browse the full peptide research catalog, lub zobacz przygotowane longevity research compounds hub.
Available Strengths
| Mocowanie fiolki | Rozmiary opakowań |
|---|---|
| 10 mg — standard research strength for in-vivo senolytic protocols and tumour-induced senescence (TIS) models; lowest per-mg cost at 20-vial pack | 10 lub 20 fiolek |
Przechowywanie i rekonstytucja
Lyophilized 2–8 °C short-term, −20 °C long-term. Reconstitute with bacteriostatic water (1.0 mL per 10 mg vial → 10 mg/mL). Avoid freeze-thaw.
FAQ
Is FOXO4-DRI the same as FOX04-DRI?
Yes — “FOX04-DRI” is a common alternative spelling where the letter “O” is written as digit “0”. The peptide is properly named after the FOXO4 transcription factor (Forkhead box O4). Both spellings refer to the same Baar/de Keizer/Demaria 2017 Cell-paper senolytic peptide.
What dose ranges have been used in published research?
The Baar 2017 paper used 1–5 mg/kg IP three times per week for 4-week cycles in aged mice. Other published protocols use 1–10 mg/kg dosing depending on model and endpoint. In-vitro work uses micromolar peptide concentrations.
Why D-amino-acid retro-inverso?
The all-D-amino-acid retro-inverse design provides essentially complete protease-resistance — host peptidases recognise only L-amino acids. This extends plasma half-life to hours and enables practical in-vivo dosing protocols that wouldn’t be feasible with the natural L-amino-acid FOXO4 sequence (which would be degraded within minutes).
Has FOXO4-DRI been in human clinical trials?
No formal Phase I/II human clinical trials of FOXO4-DRI specifically have been completed. The compound remains a preclinical research tool. Other senolytics (dasatinib + quercetin, fisetin) are in clinical-translational research separately.
What is the relationship between FOXO4-DRI and other senolytics?
FOXO4-DRI is the canonical peptide-based senolytic. Other major senolytic classes include: (a) tyrosine-kinase / BCL-2 family combinations (dasatinib + quercetin); (b) flavonoids (fisetin); (c) BH3 mimetics (navitoclax / ABT-263); (d) other p53-FOXO4-pathway interventions. The mechanisms partially overlap but target different aspects of senescent-cell survival pathways.
Other Longevity / Ageing Research Peptides
- Epitalon — Khavinson pineal-axis tetrapeptide bioregulator
- SS-31 (Elamipretide) — Cardiolipin-binding mitochondrial-targeted antioxidant peptide
- MOTS-c — Mitochondrial-derived metabolic peptide
- 5-Amino-1MQ — NNMT inhibitor — NAD-axis precursor sparing
- NAD⁺ — Direct dinucleotide pool supplementation
- BAC Water (Woda bakteriostatyczna) — Wymagany do rekonstytucji każdej liofilizowanej fiolki — sterylny rozcieńczalnik z 0,9% benzylowym alkoholem jako środkiem konserwującym
Więcej opcji w Peptydach
Ranking według liczby ostatnich zamówień MedsBase — co wybierają inni klienci w tej kategorii.
| Moc | 10 mg |
|---|---|
| Ilość | 10 fiolek, 20 fiolek, 30 fiolek |
FOXO4-DRI (FOX04-DRI) — Peptyd Badawczy o Właściwościach Senolitycznych
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FOXO4-DRI (FOX04-DRI) — Peptyd Badawczy o Właściwościach Senolitycznych
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