Hours
Proposed competition with FOXO4 for p53 in senescent cells; mechanistic proposal, not human measurement.
Protocol / Research Dosing Guide
FOXO4-DRI Research Guide: Animal Protocol, Vial Math and Safety
An evidence-organized FOXO4-DRI reference that keeps the published mouse protocol, the reported community structure, and the mechanism literature in separate, clearly labeled places.
Last reviewed September 15, 202617 minute readResearch information only
Level 2 — Animal and cell evidenceNo human trialNot FDA approved
FOXO4 Quick Start
FOXO4-DRI is a synthetic peptide built from mirror-image amino acids in reverse order, designed to resist degradation. It disrupts the FOXO4–p53 interaction so p53 can trigger apoptosis in senescent cells. All evidence is from mice and cell cultures; no human trial has been registered or completed.
Why researchers care
Senolytic research targeting the FOXO4–p53 interaction
Class
D-retro-inverso FOXO4 peptide; also sold as Proxofim
Route reported
Published animal work used intraperitoneal delivery; community use is subcutaneous
Cycle length
Not established for humans
Regulatory status
Not FDA approved; research-use only
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FOXO4 Dosing Protocol and Schedule
The supplied source separates two references: the published mouse protocol of 5 mg/kg intraperitoneally, repeated over weeks, and a reported community subcutaneous ladder of 250 mcg daily for four weeks, 375 mcg for four weeks, then 500 mcg daily. Only the first is peer reviewed, and it is an animal protocol.
| Phase or study | Amount | Frequency / evidence |
|---|---|---|
| Published animal protocol | 5 mg/kg intraperitoneal | Repeated dosing across weeks in mice |
| Reported community weeks 1–4 | 250 mcg daily subcutaneous | Reported only; no clinical validation |
| Reported community weeks 5–8 | 375 mcg daily subcutaneous | Reported only; no clinical validation |
| Reported community weeks 9–16 | 500 mcg daily subcutaneous | Reported only; no clinical validation |
The mouse amount is body-weight based and given intraperitoneally; it is not a human amount and is not convertible into one. The community ladder has never been tested for absorption, safety, or effect in people.
FOXO4 Supplies Needed
Neutral research-material planning only. This does not establish an appropriate amount or route.
Research planning item
Exact labeled research vial
Research planning item
Measured diluent volume
Research planning item
U-100 measurement reference
Research planning item
Alcohol swabs
Research planning item
Appropriate sharps container
Research planning item
Written concentration label
FOXO4 Reconstitution Calculator
Vial-format concentration math
Concentration
3.333 mg/mL
Draw volume
0.075 mL
U-100 units
7.5
Mathematical draws
40
Arithmetic only. The entered amount is not a recommendation and does not establish suitability.
Best Time to Take FOXO4: Morning or Night?
Morning or evening?
Not established. No study compared timing.
Daily or intermittent?
Animal work used repeated dosing over weeks; the reported human structure is daily. Neither is validated for people.
With food?
Not applicable to an injected format.
Missed amount?
No validated replacement or doubling procedure exists.
FOXO4 Route Comparison
| Route | What is reported | Evidence limit |
|---|---|---|
| Intraperitoneal | Published mouse protocol | Not a human route for this compound |
| Intravenous | Used in some animal work | No human data |
| Subcutaneous | Reported community use | Bioavailability and safety unstudied in humans |
| Route conversion | None available | Routes are not interchangeable |
Routes and amounts are not interchangeable unless a verified study explicitly establishes a conversion.
FOXO4 Half-Life and Dosing Frequency
| Measure | Finding | Evidence limit |
|---|---|---|
| Human half-life | Not established | No human PK study |
| Design intent | The D-retro-inverso design resists protease degradation | Resistance to degradation is not a measured half-life |
| Animal half-life | Not established in the reviewed sources | Animal work reported outcomes, not clearance |
| Frequency | Reported daily community use | Not experimentally validated |
FOXO4 Dosage Chart
| Route | Amount | Frequency | Source | Human validation |
|---|---|---|---|---|
| Intraperitoneal (mouse) | 5 mg/kg | Repeated over weeks | Published animal study | No |
| Subcutaneous | 250 mcg | Once daily | Community report | No |
| Subcutaneous | 375 mcg | Once daily | Community report | No |
| Subcutaneous | 500 mcg | Once daily | Community report | No |
Published study values describe those studies. Community-reported values are not validated dosing recommendations.
FOXO4 Reconstitution Guide
Concentration: 3.333 mg/mL
| Entered amount | Volume | U-100 units |
|---|---|---|
| 0.25 mg | 0.075 mL | 7.5 units |
| 0.5 mg | 0.15 mL | 15 units |
| 0.75 mg | 0.225 mL | 22.5 units |
- 1.Confirm the exact vial label and total quantity.
- 2.Record the measured diluent volume.
- 3.Clean the vial stopper.
- 4.Add liquid slowly along the vial wall.
- 5.Swirl gently; do not shake.
- 6.Inspect for cloudiness, discoloration, or particles.
- 7.Label the calculated concentration and preparation date.
- 8.Use the result only for arithmetic, not as a recommendation.
Reconstitution does not establish identity, purity, sterility, stability, or an appropriate amount.
How FOXO4 Works
Target
Senescent cells keep p53 sequestered in the nucleus through FOXO4; the peptide acts as a decoy that competes for that interaction.
FOXO4 Human Trials and FDA Status
Current status · verified September 15, 2026
Not FDA approved; research-use only
- The foundational 2017 mouse study designed FOXO4-DRI and reported selective senescent-cell clearance with restored fitness, fur density, and kidney function.
- A 2020 mouse study reported improved testosterone secretion after clearing senescent Leydig cells.
- Cell-culture work reported selective removal of senescent cells from expanded human chondrocyte cultures.
- No completed or registered human clinical trial of FOXO4-DRI was identified.
- There is no human pharmacokinetic, safety, or outcome data.
Who Should Avoid FOXO4?
This is an evidence-gap and precaution list, not an approved prescribing label.
Active cancer or cancer treatment
p53 and senescence pathways interact with tumor biology in complex ways
Pregnancy or breastfeeding
No data; an apoptosis-inducing agent is an unquantified risk
Active infection, recent surgery, or healing wounds
Senescent cells participate in tissue repair
Immunocompromised states
Clearance of apoptotic cells depends on immune function
Concurrent medicines
No interaction studies
Children or adolescents
No safety data
FOXO4 Side Effects, Risks and Safety
Human side effectsNone documented
Important limitation: Because no human study exists, not because none occur.
Off-target cell deathTheoretical
Important limitation: No compound is perfectly selective.
Clearance burden from dying cellsTheoretical
Important limitation: Not measured in humans.
Impaired wound healingTheoretical
Important limitation: Senescent cells contribute to repair.
Injection-site irritationReported for subcutaneous use generally
Important limitation: No compound-specific incidence data.
Product quality riskMaterial
Important limitation: D-amino acid synthesis is costly and a single wrong residue can destroy activity.
FOXO4 Timeline and Monitoring
One to three days
Proposed apoptosis of senescent cells in the animal model.
Three to fourteen days
Proposed clearance of apoptotic debris and declining SASP signaling; mouse effects were reported around ten to fourteen days.
Monitoring
No validated marker tracks activity. Inflammation panels reflect general status, not compound effect.
FOXO4 Benefits and Results: What the Evidence Shows
| Claim | Evidence level | What research shows | Important limitation |
|---|---|---|---|
| Senescent-cell clearance | Animal and cell evidence | Mouse and culture studies | No human confirmation |
| Fitness, fur density, kidney function | Animal evidence | 2017 mouse study | Mouse endpoints do not transfer |
| Testosterone in aged models | Animal evidence | 2020 mouse study | No human data |
| Human anti-aging outcomes | Not established | Marketing and extrapolation | No human trial of any kind |
FOXO4 Storage and Handling
Unreconstituted vial
Reported handling keeps the powder frozen for long-term holding; follow the exact product label.
Prepared vial
Reported handling refrigerates and uses solution within a short window; no validated stability study was located.
Sensitivity
The compound is reported to be sensitive to oxidation and repeated freeze-thaw cycles.
Appearance
A clear solution is expected after mixing; cloudiness or particles mean the material should not be used.
FOXO4 Troubleshooting
Animal mg/kg treated as a human amount
Body-weight intraperitoneal mouse amounts do not convert into a human subcutaneous amount.
Units do not match another chart
Recheck vial milligrams, liquid volume, entered amount, and the U-100 conversion.
Too much solution prepared
Prepared material is reported to degrade; prepare against actual planned use.
No observable effect
Nothing measurable is expected without a validated marker, and degraded or mislabeled material is a common confounder.
Route assumed interchangeable
Animal work used intraperitoneal and intravenous delivery; subcutaneous bioavailability is unknown.
FOXO4 Comparisons
| Compound | Class or mechanism | Evidence | FDA status |
|---|---|---|---|
| FOXO4-DRI | Peptide senolytic decoy | Mouse and cell studies | Not approved |
| Dasatinib plus quercetin | Small-molecule senolytic combination | Early human pilot studies | Not approved as a senolytic |
| Fisetin | Flavonoid senolytic candidate | Preclinical plus early human studies | Sold as a supplement |
| Epithalon | Telomere-focused peptide | Cell and animal studies | Not approved |
FOXO4 Frequently Asked Questions
What is FOXO4-DRI?
A D-retro-inverso peptide designed as a senolytic that disrupts the FOXO4–p53 interaction in senescent cells.
Why is it called DRI?
It is built from mirror-image (D) amino acids in reverse order, a design that resists enzymatic breakdown.
Is it the same as Proxofim?
Some vendors sell it under that name; verify identity through batch documentation, not the name.
Has it been tested in humans?
No. No human clinical trial was identified.
What is the published dose?
5 mg/kg intraperitoneally in mice, repeated over weeks. That is an animal protocol.
Is the community ladder validated?
No. The 250-to-500 mcg subcutaneous ladder is reported use with no clinical backing.
What is its half-life?
Not established in humans.
Is it FDA approved?
No. It is sold research-use only.
What are the main theoretical risks?
Off-target cell death, immune clearance burden, impaired wound healing, and interactions with cancer biology.
What does the calculator do?
It converts entered vial and liquid values into concentration, draw volume, and U-100 units. It does not recommend an amount.
Sources and Research
Animal research
1. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging
Foundational mouse and cell study that designed FOXO4-DRI and reported the 5 mg/kg intraperitoneal protocol.
Open direct sourceAnimal research
2. FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells
Mouse study reporting senescent Leydig cell clearance; animal evidence only.
Open direct sourceCoverage source
3. FOXO4-DRI protocol coverage source
Supplied coverage source for the reported community structure, handling, and information categories; not primary evidence.
Open direct sourceMissing information flagged for review
- Any human trial: Not established
- Human pharmacokinetics and half-life: Not established
- Subcutaneous bioavailability: Not established
- Validated human amount, cycle, and rest period: Not established
- Human safety and long-term outcome data: Not established
- Independent product identity verification: Not established