Peptide LibraryFOXO4-DRI
Also known as: Proxofim, FOXO4-D-Retro-Inverso, FOXO4 p53 disruptor
FOXO4-DRI (also called Proxofim or FOXO4-D-Retro-Inverso) is a senolytic FOXO4 peptide. FOXO4-DRI is a retro-inverso peptide — built from D-amino acids in reversed sequence — modelled on the FOXO4 region that binds p53. In senescent cells FOXO4 sequesters p53 in the nucleus, preventing it from initiating apoptosis and allowing those cells to persist despite accumulated damage.
For research use only.
Key Facts
- CAS
- 2460055-10-9
- Molecular Weight (MW)
- 5358 g/mol
- Half-life
- Experimental; not established
- FDA status
- Not Approved
- Evidence level
- Insufficient Evidence
- Human dose established
- No
- Administration Route
- Not established in humans
- Frequency
- Not established in humans
- Last updated
- Nov 7, 2026
- Reviewed
- Nov 7, 2026
- Targets
- FOXO4–p53 interaction
Vendor price snapshot
Each vendor counts once, at the median price per mg of its own listings; the typical range is the middle half of vendors. From public vendor listings collected between Oct 2026 and Nov 2026, so confirm the live price on the vendor site. Peptide Library does not sell peptides.
- Vendors listing this peptide
- 26
- Listed offers
- 37
- Median price per mg
- $14.90/mg
- Typical $12.07–$19.61/mg
Research summary
D-retro-inverso peptide designed to disrupt FOXO4–p53 binding and clear senescent cells in mice (2017 Cell paper). No CAS as a registered drug; not FDA-approved. Often sold as Proxofim.
Research evidence
- Regulatory review (FDA label)None in reviewed sources
- Controlled human trialsNone in reviewed sources
- Early or uncontrolled human studiesNone in reviewed sources
- Lab & animal studies4 reviewed sources
How it works
Each step shows whether the sources Peptide Library has reviewed include that kind of research. Counts are reviewed sources, not every study ever published. Reviews and programme summaries that describe human use are shown as "reported", not as trials, and registered trials without published results are listed but not counted. A higher step means research has progressed further; it does not mean a compound works better or is safer. Compounds whose evidence has not been reviewed yet show "Not reviewed" instead of a guess.
Peptide Library's FOXO4-DRI profile summarises 5 cited studies listed in the Science section, the compound's regulatory status, and research-protocol parameters reported for it. It is a research reference, not medical advice.
FOXO4-DRI dosage: no established human dose
FOXO4-DRI has no established human dosage. No trial of it is registered on ClinicalTrials.gov and no human study is indexed in PubMed. The published work is in cultured cells, including human cells in a dish, and in mice; the indexed abstracts of those animal studies do not state the amount given.
No established human dosage.
Human clinical evidence: None identified.
Preclinical research: FOXO4-DRI is a synthetic peptide built from D-amino acids in reverse order, designed to break the FOXO4-p53 interaction so that senescent cells die. It is a senolytic research tool. All published work is in cell culture and in mice, and the indexed abstracts generally do not state the amount given, so there is not even an animal figure to quote from most of them. No human study has given it by any route, so no human dose, route or interval is established.
Animal dosing is not converted into a human dose anywhere on this page. Where research figures appear below, they are reported as studied, not recommended.
| Human dosing established | No |
|---|---|
| Route | Not established in humans |
| Evidence level | Insufficient Evidence |
| Last reviewed | 2026-11-07 |
Preclinical and analog research
Not human dosing evidence. Listed for completeness and never extrapolated to a human dose.
| Study / context | Population | Dose | Route | Frequency | Duration | Outcome studied | Source |
|---|---|---|---|---|---|---|---|
| Preclinical — the study that designed the FOXO4 peptide, in fast-ageing and naturally aged mice (2017)Preclinical · Animal and cell study | Mice given doxorubicin, fast-ageing XpdTTD/TTD mice and naturally aged mice | Not stated in the indexed abstract; the authors say only that it was given under conditions where it was well tolerated | Not stated in the indexed abstract | — | — | Countered doxorubicin toxicity and restored fitness, fur density and kidney function in the ageing mice | Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell. 2017. |
| Preclinical — FOXO4-DRI and testosterone in naturally aged mice (2020)Preclinical · Animal and cell study | Naturally aged mice; senescent TM3 Leydig cells in culture | Not stated in the indexed abstract | Not stated in the indexed abstract | — | — | Apoptosis of senescent Leydig cells in culture, and a better testicular environment with less age-related shortfall in testosterone in the mice | FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging (Albany NY). 2020. |
| Preclinical — FOXO4-DRI in a mouse lung fibrosis model (2023)Preclinical · Animal and cell study | Mice with bleomycin-induced pulmonary fibrosis; activated fibroblasts in culture | Not stated in the indexed abstract | Not stated in the indexed abstract | — | — | Milder lung changes and less collagen deposition than in the untreated model group | FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice. Naunyn Schmiedebergs Arch Pharmacol. 2023. |
| Preclinical — FOXO4-DRI applied to human chondrocytes in culture (2021)Preclinical · Cell-culture study on human cells | Chondrocytes from healthy human donors, expanded in the laboratory | Not stated in the indexed abstract; the peptide was added to the culture, not given to a person | In vitro | — | — | Removed more than half of the heavily expanded cells and lowered senescence markers, but did not improve their ability to form cartilage | Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes. Front Bioeng Biotechnol. 2021. |
Where sources disagree
- A study on human cells is not a human study. The chondrocyte work added the peptide to cells in a dish taken from donors; nobody received it.
- Senolytic effects in mice are reported in several disease models, but one 2023 paper found that removing senescent cells could make pulmonary hypertension worse in a model, so even the direction of effect is not settled across tissues.
- The literature uses several names for this peptide, including Proxofim and FOXO4-D-Retro-Inverso, and sequence variants are reported. A dose quoted for one version is not evidence for another.
Reconstitution
Common research vial sizes: 10 mg.
| Vial | Bacteriostatic water | Concentration | Per 0.01 mL |
|---|---|---|---|
| 10 mg | 2 mL | 5 mg/mL | 50 mcg per 0.01 mL |
These figures are arithmetic only — they convert a vial and a volume into a concentration. They are not a recommendation to take any dose.
Calculate reconstitution & dose →Sequence & molecular data
| Molecular formula | C228H388N86O64 |
|---|---|
| Molecular weight | 5358 g/mol |
| CAS number | 2460055-10-9 |
| Half-life | Experimental; not established |
| Appearance | Research peptide (sequence variants reported in literature) |
| Formulation | Lyophilized Powder |
| PubChem CID | 167312269 |
Identifiers link to the public PubChem, FDA Substance Registration (UNII), ChEMBL and DrugBank records for the same entity.
Science
Mechanism of Action
FOXO4-DRI is a retro-inverso peptide — built from D-amino acids in reversed sequence — modelled on the FOXO4 region that binds p53. In senescent cells FOXO4 sequesters p53 in the nucleus, preventing it from initiating apoptosis and allowing those cells to persist despite accumulated damage. The peptide competes for that interaction, releasing p53 to translocate to the mitochondria and trigger apoptosis. Because the FOXO4-p53 interaction is markedly more important in senescent than in healthy cells, the effect is relatively selective for senescent fibroblasts, which is what makes it a senolytic. The retro-inverso construction confers protease resistance. Evidence comes from the original mouse work; there are no human trials.
Origin
Synthetic D-retro-inverso peptide (Baar et al., Cell 2017).
Targets
Studies
- The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI
- FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway
- FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation
- FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells
- FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice
Research statistics
14 PubMed publications · 0.0% human clinical research · 0 registered trials
Counts of published research through 2026-11-01, not evidence that it works. Publications by year, study types and trials · How publications are counted
Regulatory & research status
FOXO4-DRI is not an FDA-approved product. It is sold for laboratory research and has no approved medical use.
| FDA status | Not Approved |
|---|---|
| Availability | Research-Only |
| WADA (sport) | Banned in Sport |
| Library classification | Research-Only |
How FDA approval, compounding and research-only status differ
Benefits
FOXO4-DRI side effects
FOXO4-DRI has no controlled human safety data. The effects below are reported, not established, and absence from the list is not evidence of safety.
Side Effects
- No established human dose
- On-target p53 risks theoretical
Storage & stability
Lyophilized (freeze-dried) peptide powder is far more stable than the reconstituted solution. Keep sealed vials cold, dry and away from light; long-term storage is typically frozen, with short-term refrigeration for vials in use.
Once reconstituted in bacteriostatic water, keep the solution refrigerated, avoid repeated freeze–thaw cycles and agitation, and label the vial with the reconstitution date and concentration. Discard any solution that turns cloudy or shows particulates.
Degradation rates differ by sequence: peptides containing methionine, cysteine, asparagine or glutamine are more prone to oxidation and deamidation, so shelf life after reconstitution is compound-specific rather than universal.
Read the full guide: how to store peptides before and after reconstitution →
Source: Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharm Res. 2010;27(4):544–575. (PMID 20143256). General guidance for research handling; not product-specific instructions.
FOXO4-DRI: frequently asked questions
What is FOXO4-DRI?
D-retro-inverso peptide designed to disrupt FOXO4–p53 binding and clear senescent cells in mice (2017 Cell paper). No CAS as a registered drug; not FDA-approved. Often sold as Proxofim.
How does FOXO4-DRI work?
FOXO4-DRI is a retro-inverso peptide — built from D-amino acids in reversed sequence — modelled on the FOXO4 region that binds p53. In senescent cells FOXO4 sequesters p53 in the nucleus, preventing it from initiating apoptosis and allowing those cells to persist despite accumulated damage.
Is FOXO4-DRI FDA approved?
No. FOXO4-DRI is not approved by the FDA for any indication and is categorised as research-only. It has not been reviewed for safety or efficacy as a medicine, and published research should be read as investigation rather than established use.
What is the half-life of FOXO4-DRI?
Reported half-life for FOXO4-DRI is Experimental; not established. Half-life describes how long the compound persists in circulation, not how long any effect lasts, and published figures vary with route of administration, formulation and the population studied.
Is FOXO4-DRI banned in sport?
FOXO4-DRI is recorded here as prohibited in sport. Athletes subject to anti-doping rules should check the current WADA Prohibited List directly, since it is revised annually and classifications change.
What peptides are similar to FOXO4-DRI?
Compounds most often compared with FOXO4-DRI include Epitalon, Pinealon, Klotho and NAD+ (Nicotinamide Adenine Dinucleotide). They are grouped by shared mechanism or research area rather than by equivalence, and their regulatory status and evidence base differ.
References
- The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI — Nat Commun, 2025External reference
- FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway — Front Bioeng Biotechnol, 2025External reference
- FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation — Commun Biol, 2025External reference
- FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells — Exp Gerontol, 2024External reference
- FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice — Naunyn Schmiedebergs Arch Pharmacol, 2023External reference
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Compiled by Peptide Library Editorial · Reviewed Aug 30, 2026 · Updated Nov 7, 2026 · Version 2
This FOXO4-DRI profile is compiled from published literature (5 cited studies linked above), public regulatory records and chemical registries. It describes what research reports; it is not medical advice, and nothing here is a dosing recommendation for humans. Peptide Library does not sell peptides. Editorial policy · How profiles are compiled · Report an error
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