Important limitations
- Individual claims and source links have not yet completed editorial verification.
- Evidence level, applicable study model, formulation, route and population remain unassigned.
FOXO4-DRI
FOXO4-DRI targets senescent cells by disrupting FOXO4-p53 signaling, advancing longevity and regenerative research.
Dosing & scaling, explained
The moderated mass amounts below are retained for comparison. Near-duplicates, mix-dependent volumes and device markings are excluded. This is educational source context, not a protocol or recommendation.
Mass amounts available for comparison
- Lower range1 mgDose
Recorded example with no verified study backing; shown for amount literacy only.
- Mid range5 mgDose
Recorded example with no verified study backing; shown for amount literacy only.
Only mcg or mg amounts are retained. The calculator derives mL, syringe units or pen clicks from the current vial strength, water volume and device.
No independently verified schedule
Evidence context
No clinical amount or schedule is inferred from this material. Source verification is pending, and every displayed amount remains educational context rather than guidance.
Storage, handling and interpretation
Product identity
Verify the exact compound, formulation and amount against the product label or certificate before calculation.
Storage & handling
Follow the product label, certificate and validated laboratory SOP; no universal storage assumption is applied here.
Prepared solutions
Label concentration and preparation date, use sterile technique where applicable, and follow a validated stability protocol.
Reported protocols for FOXO4-DRI
What published studies and recent community write-ups report about amounts, timing and course length. 4 preclinical and 5 community-reported rows, each linked to its source. These are descriptions of what others report, not instructions, and nothing here is medical advice.
| Context | Dose | Frequency | Route | Course | Source |
|---|---|---|---|---|---|
| Preclinical4 rows | |||||
| Original mouse senolytic protocol (chemotherapy, fast-aging and naturally aged mice)Mice given doxorubicin, fast-aging XpdTTD/TTD mice and naturally aged (110+ weeks) p16::3MR mice | 5 mg/kg per injection | Every other day for three doses (days 1, 3 and 5) | Intravenous in the doxorubicin model; intraperitoneal in the aged-mouse comparisons with ganciclovir | One 5-day course; readouts at 18-21 days (running wheel) and 30 days (fur, kidney markers)No repeat courses were run | Cell (PubMed Central)2017 |
| Three 5 mg/kg injections reduced p16-driven senescence signal, restored fur density and responsiveness, and lowered plasma urea and creatinine in aged mice, without changing body weight, kidney weight or platelet counts at 30 days. The authors cautioned against permanent FOXO4 inhibition because FOXO4 has a normal role in the DNA-damage response, and nothing in this paper involves humans. | |||||
| Aged-testis senolytic studyNaturally aged male mice (20-24 months), 6 per group | 5 mg/kg in PBS | Every other day for three injections | Intraperitoneal | One 5-day course, assessed 30 days laterNot applicable | Aging (PubMed Central)2020 |
| Thirty days after the three injections, serum testosterone and the steroidogenic proteins 3beta-HSD and CYP11A1 were higher in treated mice than in PBS controls, with no difference in body or testis weight. The result rests on six animals per group and a single time point. | |||||
| Bleomycin lung fibrosis modelC57BL/6 mice with bleomycin-induced pulmonary fibrosis | 5 mg/kg | Three injections on days 14, 16 and 18 after bleomycin | Intraperitoneal | One course; lungs examined on day 21Not applicable | Journal of Cellular and Molecular Medicine (PubMed Central)2022 |
| Started after fibrosis was already established, three injections reduced senescent-cell burden, SASP markers, collagen deposition and myofibroblasts to a degree the authors compared with 20 oral doses of 300 mg/kg pirfenidone. It is a short mouse study with no survival or lung-function endpoint. | |||||
| Vascular aging study with a one-month courseNaturally aged mice (17 months) and D-galactose-induced aging mice, at least 5 per group | 5 mg/kg | Every 2 days | Intraperitoneal | 1 month (about 15 injections)None described | Frontiers in Bioengineering and Biotechnology2026 |
| This is the longest published exposure: a month of alternate-day injections lowered aortic senescence markers, inflammatory cytokines and pulse-wave velocity, and thinned the aortic wall, in both aging models. It extends the three-dose design to repeated dosing but still reports no toxicology or human data. | |||||
| Community-reported5 rows | |||||
| Three-injection pulse course (community chart) | 1 mg (conservative), 2.5 mg (most reported) or 3.3 mg (full 10 mg vial) per injection | Days 1, 3 and 5, then stop | Subcutaneous, abdomen or thigh, rotating sites | One 5-day course3-6 months off before any repeat; 6 months after a full-vial course | Community resource2026 |
| This 2026 chart copies the every-other-day spacing of the mouse work onto 1-3.3 mg subcutaneous doses drawn from a 10 mg vial in 2 mL (20, 50 or 66 units). It states plainly that the milligram figures are price-driven convention, that a body-surface-area conversion of the mouse dose would be roughly 28 mg per injection, and that no study has ever used the subcutaneous route. | |||||
| Two-week 5-on/2-off course (community standard) | 1 mg (20 units at 5 mg/mL); 2 mg described as an advanced tier | Once daily in the morning, 5 days on and 2 days off | Subcutaneous | 2 weeks (one 10 mg vial)3-6 months rest; repeated 2-3 times per year | Community resource2026 |
| A retailer's April 2026 guide presents 1 mg daily on weekdays for two weeks as the most documented community pattern, and separately lists an aggressive weight-based 2-5 mg/kg protocol that it criticizes for skipping allometric correction (which would put the human equivalent near 12-30 mg). It reports flu-like malaise and injection-site reactions as the commonly described side effects and stresses that no human trial exists. | |||||
| 16-week daily ladder (community) | 250 mcg daily (weeks 1-4), 375 mcg daily (weeks 5-8), 500 mcg daily (weeks 9-16) | Once daily | Subcutaneous | 16 weeks (about 45 mg, 5-7 vials of 10 mg)None described | Community resource2026 |
| Unlike the pulse protocols, this site reports a slow daily microdose ladder reconstituted at 10 mg in 3 mL (about 3.33 mg/mL). It labels the ladder as reported community context, notes that reconstituted stability is uncertain, and repeats that the only published dosing is 5 mg/kg intraperitoneally in mice. | |||||
| Tiered community protocols compared | 1 mg (low), 2-3 mg (mid-range), 10-25 mg (high) per injection | Low tier once daily 5 on/2 off; mid and high tiers every other day for three doses | Subcutaneous most common; intravenous reported in some clinics | 2 weeks (low tier) or 5-6 days (mid and high tiers)Low tier repeated 2-3 times a year with 3-6 months between; mid tier every 2-6 months | Community resource2026 |
| This June 2026 review sets the three circulating tiers side by side and notes that the high tier is 5-25 times the low one with no human evidence for safety or need. It also records that there are zero registered or published human trials, that the inventor has discouraged self-experimentation, and that the often-quoted 10:1 selectivity figure comes from interviews rather than a published dose-response study. | |||||
| Allometric translation and the full community range | 1-25 mg per injection (community); about 25-30 mg per dose if the mouse dose is scaled by body surface area | Daily or every other day | Subcutaneous (community); intraperitoneal in the mouse studies | 1-3 weeksNot specified | Community resource2026 |
| One community guide frames the 25-fold spread in community doses as evidence of missing pharmacology rather than individual variation, and points out that the allometric conversion assumes equal bioavailability across routes, which has not been shown. It lists the compound as not explicitly named on the 2025-2026 WADA list and notes that Cleara Biotech's candidates had not entered trials as of early 2026. | |||||
How a course is commonly described
- Days 1, 3 and 5Community-reported
Community pulse protocols give three subcutaneous injections of 1-3.3 mg on alternate days and then stop, mirroring the spacing of the mouse experiments. Guides describe no acute effect in the first hours, with cellular uptake in the animal work seen within 2-4 hours.
- Days 2-10Community-reported
Self-reports place mild flu-like malaise, fatigue or achiness 24-72 hours after a dose, which guides attribute to clearance of dying cells; none of this has been measured in a trial. Two-week community courses continue 1 mg weekday dosing through this window instead of stopping after day 5.
- Weeks 3-4Preclinical
In the original mouse study every functional endpoint was read well after dosing ended: running-wheel activity at days 18-21 and fur score, responsiveness, plasma urea and creatinine at day 30. Community guides borrow this timing to suggest when any change would be expected.
- Months 3-6: breakCommunity-reported
Guides describe long gaps of 3-6 months between courses, with 2-3 courses a year at most, reasoning that a senolytic removes a finite cell population and that chronic FOXO4 inhibition was discouraged by the original authors. No source has measured how quickly senescent cells re-accumulate in people.
- Repeated-dosing comparisonPreclinical
The only published course longer than three doses is a 2026 mouse study that injected 5 mg/kg intraperitoneally every 2 days for a month and read aortic markers at the end. It did not test repeat cycles or report toxicology, so it offers no basis for any human schedule.
- No human has received FOXO4-DRI in a registered trial, so every dose, route and interval above is either a mouse protocol or a community convention. Published mouse dosing was intravenous or intraperitoneal; nobody has measured how much of a subcutaneous dose reaches circulation.
- The 1-3.3 mg community doses are roughly a tenth of what a body-surface-area conversion of the 5 mg/kg mouse dose would give (about 28 mg per injection for a 70 kg adult). Community sources themselves say cost, not evidence, set the usual dose.
- FOXO4-DRI is not approved by any regulator and has no compounding pathway; the Cell authors advised against sustained FOXO4 inhibition because FOXO4 participates in normal DNA-damage repair. The rows record what sources report, not recommendations.
Sources for this section (9)
- Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging
- FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice
- FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway
- FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway
Plus 5 community resources (dosing guides, forum threads and vendor write-ups), reported above but not linked.
Overview
FOXO4-DRI is a synthetic 46-amino-acid peptide built from D-amino acids in a retro-inverso arrangement, pairing a fragment of the FOXO4 forkhead domain with an HIV-TAT cell-penetrating tail so that it resists proteases and enters cells. It was designed by Peter de Keizer's group at Erasmus MC and described in Cell in 2017 as a senolytic: it blocks the FOXO4 to p53 interaction that keeps senescent cells alive, freeing p53 to trigger apoptosis in those cells. Every efficacy result comes from mouse models (chemotherapy-induced senescence, fast-aging XpdTTD/TTD mice, naturally aged mice, aged testes, bleomycin lung fibrosis, vascular aging) and from cell culture. No human trial has been registered or published, no regulator has approved it, and the spin-out Cleara Biotech has moved on to next-generation candidates, so the compound sold online (sometimes as Proxofim) is an unregulated research chemical with no human dose, safety or pharmacokinetic data.
What researchers are exploring
These themes organize the educational information currently available. Individual claims remain under source review and are not treatment claims.
- 1
Retro-Inverso Engineering
Why D-amino acids matter
- 2
Senescent Cell Clearance
Mechanism and health-span outcomes
- 3
Metabolic & Proteostasis Insights
FOXO signaling beyond senescence
- 4
Cardiovascular & Neurodegenerative Studies
Aging tissues and proteasome support
- 5
Summary
Research considerations
What is known and what still needs verification
Available context is organized without assigning unsupported study models or evidence grades.
- Not graded
Retro-Inverso Engineering
Why D-amino acids matter
- Not graded
Senescent Cell Clearance
Mechanism and health-span outcomes
Amounts recorded for FOXO4-DRI
These amount records are independent from vial strength, reconstitution volume and measuring device. A recorded source is not the same as study backing, and these values are not recommendations.
- 1Dose · lower endpointSign in for schedule, duration and source context.1 mg
- 2Dose · upper endpointSign in for schedule, duration and source context.5 mg
Chemistry identifiers
Sequence, synonyms and registry identifiers as recorded in PubChem, the National Library of Medicine's open chemistry database. Formula, mass and CAS number are summarized at the top of the page.
Sequence
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-Gly-D-Trp-D-Ala-D-Asn-D-Arg-D-Arg-D-Ser-Gly-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-Gly-OH
Also listed as
FOXO4-DRI, FOXO4 D-retro-inverso peptide, Proxofim (vendor name), FOXO4-DRI TFA salt form (PubChem synonym), Pepscan FOXO4-DRI (Baar et al. 2017)
InChIKey
WVZCDZFJLXBWHG-XXZPGMBKSA-N
IUPAC name
(4R)-5-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-5-amino-1-[[(2R)-4-amino-1-[[2-[[(2R)-1-[[(2R)-1-[[(2R)-4-amino-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[2-[[2-[[(2R)-6-amino-1-[[(2R)-1-[(2R)-2-[(2R)-2-[(2R)-2-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-5-amino-1-[[(2R)-1-[[(2R)-1-[[(2R)-6-amino-1-[[(2R)-6-amino-1-[[(2R)-5-carbamimidamido-1-(carboxymethylamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1,4-dioxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-[[(2R)-2-[[(2R,3R)-2-[[(2R)-2-[[(2R)-5-amino-2-[[(2R)-2-[[(2R,3R)-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-[[(2R)-1-[(2R)-2-[[(2R)-6-amino-2-[[(2R)-2-[[(2R)-2-[[(2R,3S)-2-[[(2R)-2-amino-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-4-carboxybutanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]-3-hydroxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-methylpentanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-oxopentanoic acid
Limitations and unknowns
Sources
1 link carried over from the earlier page, awaiting verification.