Dashnaiv Peptides
Compounds·senolytic & cytoprotective·FOXO4-p53 interaction disruptor, senolytic

FOXO4-DRI: the senolytic peptide that has never been given to a person, what it did in mice, and why it stalled

What 19 indexed publications and 0 randomized trials actually state about foxo4-dri, sentence by sentence, each tied to its source and labeled by the kind of evidence it is.

Animal, preclinical Reviewed 19 sources Updated

At a glance

Evidence availability
Preclinical only
Animal and cell studies, no human data
Indexed publications
19
Europe PMC, title or abstract, 2026-09-14
Human studies in ledger
0
0 randomized; study count, not efficacy proof
Approval
none found
no registered development programme
Routes reported
intraperitoneal
from studies in this ledger
Studied in
Humans, Mice, Rats; human autopsy tissue
13 primary studies in the evidence table
Reviewed by Adam Mirando, PharmD, on . What changed

What FOXO4-DRI is, and how far it has got

FOXO4-DRI is a synthetic peptide designed in 2017 to kill senescent cells by breaking the FOXO4-p53 interaction that keeps them alive. Europe PMC indexes 19 publications naming it or a listed alias, and none of them is a study in a person: the entries that mention humans used cells in culture, cultured tissue, isolated proteins and autopsy lungs. The evidence that exists is in mice, where the original study restored fitness, fur density and kidney function in aged animals, and later work reported better testosterone and spermatogenesis, less lung fibrosis, less radioresistance in lung cancer and less vascular ageing.

Nine years on there is no first-in-human study, no registered trial and no measured half-life, and the company founded on the work has moved towards the protein interaction rather than this molecule. It is sold as a research chemical, often under the name Proxofim.

What the evidence level means

Publication counts show what is indexed, not how strong the evidence is. The ledger below separates human clinical records from preclinical, analytical, and in-vitro work.

Human clinical studies in this ledger00 randomized · 0 other human clinical
Evidence strengthAnimal and cell studies, no human dataSeparate from evidence availability
Efficacy signalNot evaluated in humansRead the study result, not the tier alone

Human-study result: No person has received FOXO4-DRI in a study. The ledger's strongest results are in mice: restored fitness, fur density and kidney function in aged animals in 2017, better testosterone and spermatogenesis in aged mice, and less fibrosis, less radioresistance and less vascular ageing in disease models.

Interpretation boundary: An indexed publication count is a discovery measure. It does not establish efficacy, safety, approval, or a personal treatment plan.

FOXO4-DRI in two minutes

What it is. A synthetic peptide designed in 2017 in Rotterdam to kill senescent cells, the damaged cells that stop dividing, refuse to die and accumulate with age. It works as a decoy that frees the protein p53 so those cells can finally self-destruct.

What the research shows. 19 indexed publications, and not one of them is a study in a person. The ledger's human-labelled entries are human cells in a dish and human autopsy lung tissue. In mice the 2017 paper restored fitness, fur density and kidney function in aged animals; later mouse work reported better testosterone and sperm quality, less lung fibrosis, less radioresistance in lung cancer and less vascular ageing.

What is missing. Everything downstream of the mouse. No first-in-human study, no registered trial, no measured half-life, no blood test that shows whether it worked, and no published analysis of what is in the vials sold online.

What happened to the development. A company was founded on the original work and has moved towards the underlying protein interaction rather than this molecule. Nine years on, the peptide is mostly a laboratory tool other groups use to study senescence in fibrosis, scarring, glioblastoma and newborn lung disease.

Where the evidence is thinnest. Human safety, which is not thin but absent; and the schedules that circulate online, which correspond to no experiment.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

The human trial that does not exist

This is the whole answer to the question most people arrive with, so it goes before anything else.

Searches for FOXO4-DRI human trial return papers, blog posts and vendor pages, none of which describe a trial. There has never been one. There is no completed study, no ongoing study and no registered study in any trial registry, nine years after the paper that introduced the peptide.

What confuses the picture is that several papers do involve human material. They are worth separating:

Every study in this ledger that involves human material, and what the material was.
StudyWhat was human about itWhat it was not
Huang 2021, chondrocytesCartilage cells taken from healthy donors and expanded in cultureNobody received the peptide; it was added to a flask
Kong 2025, keloid scarsKeloid tissue and fibroblasts cultured outside the bodyAn organ culture, not a patient treated
Bourgeois 2025, structureHuman p53 and FOXO4 protein domains in a nuclear magnetic resonance tubeProtein chemistry, with no cells and no animal
Jing 2024, newborn lung diseaseAutopsy lungs from infants, compared with the rat modelThe peptide went into rat pups; the human lungs were only examined

So the correct count of people who have received FOXO4-DRI in a published study is zero. The correct count who have received it outside one is unknown and unmeasurable, because nobody collects it. A 2026 review of the FOXO4-p53 axis in brain ageing makes the same point from the other direction: when it looks for preliminary human evidence, it has to cite trials of fisetin, a different and orally available compound, because there are none of this peptide to cite.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

How it works: a decoy that frees p53

Written from general pharmacology and the development record, and marked as editorial synthesis; the measurements behind it are quoted in the biomarker section.

  • Senescent cells are cells that have stopped dividing after damage but refuse to die, and accumulate with age while leaking inflammatory signals into the tissue around them. They survive by holding p53 in the nucleus, where it cannot start the cell-death programme, and the protein that holds it there is FOXO4. That is the interaction the 2017 Rotterdam group set out to break.Editorial synthesis
    Editorial synthesis from general knowledge
  • FOXO4-DRI is a decoy. It carries the stretch of FOXO4 that binds p53, so it competes for the same site and releases p53, which then moves out of the nucleus and triggers the intrinsic apoptosis pathway. Healthy cells do not depend on that interaction to stay alive, which is the basis of the selectivity claim: in the original paper the peptide killed senescent cells while leaving others largely alone. The 2026 endothelial study traced the same sequence through p53, BAX and cleaved caspase-3.Editorial synthesis
    Editorial synthesis from general knowledge
  • The DRI in the name is the engineering. D-retro-inverso means the peptide is built from mirror-image D-amino acids assembled in reverse order, which presents roughly the same shape to its target while being unrecognisable to the enzymes that break down ordinary peptides. A cationic cell-penetrating sequence is attached to carry it inside cells. The 2025 structural work showed that this delivery sequence is not merely a passenger: it contributes to the binding itself, which is one reason a 2025 group designed a shorter L-amino-acid successor rather than pursuing this molecule.Editorial synthesis
    Editorial synthesis from general knowledge

Study by study: what FOXO4-DRI did, and in what

The full ledger, sorted by species. Read the middle column first: it is what the study actually was.

Every primary study of FOXO4-DRI in this record's ledger.
StudySpecies or materialWhat it found
Baar 2017 (the paper that designed it)Mice, aged and fast-ageingSelective killing of senescent cells; restored fitness, fur density and kidney function; blunted the toxicity of doxorubicin
Zhang 2020Mice, naturally agedCleared senescent Leydig cells; improved the testicular environment and age-related testosterone decline
Li 2024Mice, naturally agedBetter sperm quality and spermatogenesis, via less secretion from senescent Leydig cells
Meng 2021Mice, lung cancer modelKilling senescent cancer-associated fibroblasts made tumours more sensitive to radiotherapy and reduced radiation-induced lung fibrosis
Liu 2023Mice, bleomycin lung fibrosisMilder damage and less collagen deposition than untreated model animals
Han 2022Mice, bleomycin lung fibrosisComparable to the approved drug pirfenidone on senescent-cell and secretory measures in that model
Hu 2026Mice, aged and progeroidSuppressed aortic ageing and improved aortic function, through p53, BAX and caspase-3
Jing 2024Rat pups, hyperoxic lung injuryFour doses over one week gave outcomes similar to two other protective agents
Ning 2026Glioblastoma modelsCleared cells made senescent by temozolomide and improved that drug's effect
Huang 2021Human cartilage cells in cultureRemoved more than half the cells in an aged culture while barely touching a young one
Kong 2025Human keloid tissue in cultureApoptosis in senescent scar fibroblasts, with p53 leaving the nucleus
Bourgeois 2025Protein structure, no cellsMapped how the peptide binds p53, and found the delivery sequence contributes to binding
Deryabin 2022Cells in cultureUsed FOXO4-DRI as the comparator while proposing a different way to kill senescent cells

Two patterns are worth naming. The first is that the disease models outnumber the ageing studies: most groups use this peptide as a way to ask whether senescent cells matter in their disease, and the answer being published is about the disease, not about the peptide as a treatment. The second is that every one of these is an endpoint measurement in tissue. Not one reports how long the peptide lasted, what dose gave what effect, or what happened to the animals afterwards.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

What the evidence shows

One row per primary study in this record's ledger. Fields are read from each paper's indexing and abstract. "Analytical method" marks papers about detecting or measuring the compound rather than about its effects.

13 primary studies in this record's ledger, strongest evidence first. A dash means the abstract did not state the value.
StudyDesignnSpeciesDoseRouteDurationReported outcomeTier
Jing 2024 Rat model, with human autopsy lungs examined alongside — Rats; human autopsy tissue—intraperitoneal— Cellular senescence increased in rat and human BPD lungs, as evidenced by increased oxidative DNA damage, tumor suppressors, GL-13 stain, and inflammatory cytokines with decreased cell proliferation and lamin B… Observational, human
Ning 2026 Animal study — ———— Mechanistically, AGK suppression amplified TMZ-induced CSEN through increasing mitochondrial ROS (mtROS) and decreasing membrane potential. Animal, preclinical
Hu 2025 Animal study — Mice—intraperitoneal— Injection of FOXO4-DRI in both naturally aged and induced aging mice effectively suppressed aortic aging and improved aortic function. Animal, preclinical
Han 2022 Animal study — Mice——— We found that similar as the approved medication Pirfenidone, FOXO4-DRI decreased senescent cells, downregulated the expression of senescence-associated secretory phenotype (SASP) and attenuated BLM-induced… Animal, preclinical
Meng 2021 Animal study — Mice——— In conclusion, by targeting senescence, we offer a strategy that simultaneously decreases radioresistance of NSCLC and the incidence of RIPF. Animal, preclinical
Zhang 2020 Animal study — Mice——— In naturally aged mice, FOXO4-DRI improved the testicular microenvironment and alleviated age-related testosterone secretion insufficiency. Animal, preclinical
Bourgeois 2025 In vitro study — Humans——— — Mechanistic, in vitro
Kong 2025 In vitro study — Humans——— We further demonstrate that a senolytic FOXO4-D-retro-inverso-isoform peptide (FOXO4-DRI) promotes apoptosis and decreases G0/G1 phase cells in pro-senescence models of keloid organ cultures and fibroblasts,… Mechanistic, in vitro
Deryabin 2022 In vitro study — ———— According to our data, the higher sensitivity of senescent cells compared to the control ones towards nigericin-induced death was partially mediated by the lower intracellular K + content in senescent cells and by… Mechanistic, in vitro
Huang 2021 In vitro study — ———— Results showed that the treatment of FOXO4-DRI removed more than half of the cells in PDL9 but did not significantly affect the cell number of PDL3 chondrocytes. Mechanistic, in vitro
Baar 2017 Animal study, mice — Mice5 mg/kg intraperitoneal (methods, not abstract)intraperitonealcycles over weeks Under conditions where it was well tolerated in vivo, this FOXO4 peptide neutralized doxorubicin-induced chemotoxicity. Moreover, it restored fitness, fur density, and renal function in both fast aging XpdTTD/TTD and naturally aged mice. Animal, preclinical
Li 2024 Animal study, mice — Mice——— In naturally aged mice, FOXO4-DRI-treated aged mice exhibited increased sperm quality and improved spermatogenesis. Animal, preclinical
Liu 2023 Animal study, mice — Mice——— The animal group of FOXO4-DRI therapeutic administration shows a milder pathologic change and less collagen deposition compared with the BLM-induced group. Animal, preclinical

Doses reported in studies

Each entry is a sentence quoted from the study's abstract, with the study's design, sample size and year in front of it. Comparator doses in the same sentence are not attributed to foxo4-dri.

  • No abstract in this ledger states a dose. The 2017 paper that designed the peptide gave it to mice intraperitoneally at 5 milligrams per kilogram, in cycles of three doses repeated over weeks; that figure sits in the paper's methods rather than its abstract, so it is recorded here as editorial until the full text is in the ledger. Every other study reports that the peptide was administered and leaves the amount to its methods section.Editorial synthesis
    Editorial synthesis from general knowledge · primary document to be added to the ledger
  • Rat model rats 2024 Animal, preclinical
    Foxo4 dri administered at P4, P6, P8, and P10 led to outcomes similar to TUDCA and KYC.
    Source pmid-37874230 · quoted verbatim from the abstract

Every dose in the studies, and the species that received it

There are two numbers in this whole literature. Both were given to rodents by a route nobody uses at home.

Doses of FOXO4-DRI as published.
SettingSpeciesRouteDoseSchedule
Baar 2017, the original studyMiceIntraperitoneal5 mg/kg (stated in the methods, not the abstract)Three doses per cycle, cycles repeated over weeks
Jing 2024, newborn lung injuryRat pupsIntraperitonealNot stated in the abstractPostnatal days 4, 6, 8 and 10
Every other studyMice, rats or cellsIntraperitoneal or in cultureNot stated in the abstractNot stated in the abstract
Any human study——None exists—

The schedules that circulate online are built on neither number. They describe a few hundred micrograms a day by subcutaneous injection, laddered over several weeks. Set against the mouse regimen, converted between species the way pharmacologists convert it, that is smaller by roughly two orders of magnitude, and by a different route.

That gap is worth stating plainly because it cuts against the page it usually appears on. A schedule that cites the 2017 mouse work as its evidence is not a cautious version of that experiment; it is a different intervention, and the mouse result cannot be claimed for it. It is equally not an argument for taking more. Nothing establishes that any dose of this peptide is safe in a person, the species gap runs in both directions, and the mouse studies were looking for benefit rather than for harm. The honest summary is that the dose question has no answer yet, in either direction.

If you are reading this page because you want the arithmetic for a vial, the reconstitution calculator does the volume maths for any peptide, and says nothing about whether a figure should be used.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Side effects: what is known, which is almost nothing

There are no human safety data at all. What the mouse papers report is that the peptide was tolerated at the doses they used; what they did not do is look for harm systematically, in a species whose senescent cells also help wounds heal. Events and their frequency as each study reported them, with the denominator where the abstract gives one.

  • Animal study mice 2017 Animal, preclinical
    Under conditions where it was well tolerated in vivo, this FOXO4 peptide neutralized doxorubicin-induced chemotoxicity.
    Source pmid-28340339 · quoted verbatim from the abstract
  • There are no human safety data of any kind, because no person has received it in a study. Tolerability in a mouse over weeks is not a safety assessment; the mouse papers looked for benefit and reported no obvious harm, which is a different thing from looking for harm. The concerns that follow from the mechanism have not been tested in anything: senescent cells are needed transiently for wound healing and tissue repair, so clearing them indiscriminately has a plausible cost; a peptide that frees p53 to trigger cell death is acting on the central apoptosis switch; and the 2025 structural work found that the cationic cell-penetrating part of the molecule contributes to binding, which is also the part that gets it into every cell rather than only senescent ones.Editorial synthesis
    Editorial synthesis from general knowledge · primary document to be added to the ledger
  • Product quality is a separate and unmeasured risk. The molecule is built entirely from D-amino acids in reverse sequence, which makes it expensive and difficult to synthesise correctly, and nothing sold under the name has been assessed by a regulator. No published analysis of vials sold online exists, unlike the analyses that have been done for other compounds on this site.Editorial synthesis
    Editorial synthesis from general knowledge · primary document to be added to the ledger

Who FOXO4-DRI is discussed for, and what is unresolved

Studied in: aged mice, mouse disease models, rat pups, and human cells in culture. Never studied in: any person, at any age, for any indication. Discussed by: the longevity community, people who found it through the 2017 coverage, and vendors selling it as Proxofim.

The open questions are not cautions drawn from experience, because there is no experience. They follow from the mechanism:

  • Senescent cells are not only harmful. They appear transiently during wound healing and tissue repair, and clearing them without regard to timing has a plausible cost that no study has measured.
  • Selectivity is a claim about cell culture and mice. The delivery sequence carries the peptide into everything; the selectivity comes from what the cell depends on, and it has never been tested in a human tissue in a living body.
  • There is no way to check. Senescence is measured in tissue, not in blood. Nobody taking this compound can know whether anything happened.
  • Cancer cuts both ways. The same papers show senescent cells protecting tumours from treatment, and other work shows senescence restraining tumour growth. Clearing senescent cells in someone with an undetected cancer is unstudied.
  • The vial is unknown. An all-D-amino-acid peptide is hard to make correctly, and no independent analysis of what is sold has been published.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Biomarkers measured in studies

Laboratory and clinical measures the studies report tracking, including which hormones did and did not change.

  • Animal study mice 2022 Animal, preclinical
    Furthermore, FOXO4-DRI could increase the percentage of type 2 alveolar epithelial cells (AEC2) and fibroblasts, and decrease the myofibroblasts in bleomycin (BLM)-induced PF mouse model.
    Source pmid-35510614 · quoted verbatim from the abstract
  • In vitro study humans 2025 Mechanistic, in vitro
    We further demonstrate that a senolytic FOXO4-D-retro-inverso-isoform peptide (FOXO4-DRI) promotes apoptosis and decreases G0/G1 phase cells in pro-senescence models of keloid organ cultures and fibroblasts, accompanied with p53-pS15 nuclear exclusion.
    Source pmid-39994346 · quoted verbatim from the abstract
  • What the studies count is senescent cells and the signals they secrete: p16, beta-galactosidase staining, the senescence-associated secretory phenotype, and apoptosis markers in the tissue itself. None of that can be measured from a blood sample, which is the practical problem with the compound. There is no established blood test that shows whether a senolytic has worked in a person.Editorial synthesis
    Editorial synthesis from general knowledge

Reported interactions

Sentences in which the compound is studied alongside another agent. Read the quotation: the word interaction can also be statistical.

  • Animal study mice 2021 Animal, preclinical
    Specific induction of senescence-like CAF apoptosis using FOXO4-DRI, a FOXO4-p53-interfering peptide, resulted in remarkable effects on radiosensitizing NSCLC cells in vitro and in vivo.
    Source pmid-34877934 · quoted verbatim from the abstract
  • Animal study 2026 Animal, preclinical
    Mito-TEMPO, a mtROS scavenger, and FOXO4-DRI, a senolytic agent, both enhanced the therapeutic efficacy of TMZ by eliminating these senescent cells via apoptosis.
    Source pmid-42391447 · quoted verbatim from the abstract
  • The only agents the peptide has been given alongside are cancer treatments, in the studies that used it to kill cells the treatment had made senescent: doxorubicin in the 2017 mouse work, radiotherapy in the 2021 lung-cancer study and temozolomide in the 2026 glioblastoma study. Those are experiments in which senescence is the target, not interaction studies. No study has examined it with any other drug, and none has looked at what it does in an animal receiving ordinary medicines.Editorial synthesis
    Editorial synthesis from general knowledge

Reported timelines

Onset, peak and duration figures as each study reported them.

  • Nothing in this ledger reports an onset, a peak or a duration of effect. The studies measure tissue at the end of an experiment, not a time course, and no pharmacokinetic study of the peptide has been published in any species. The D-retro-inverso design is intended to resist enzymatic degradation, which is a design goal rather than a measured half-life.Editorial synthesis
    Editorial synthesis from general knowledge · primary document to be added to the ledger

What is measured over time, and what is not

Nothing in this literature is a time course. The mouse studies dosed in cycles across weeks and then measured tissue at the end; the newborn rat study gave four doses across one week. No study reports an onset, a peak, a duration of effect or a half-life, in any species. The D-retro-inverso design exists to resist the enzymes that would destroy an ordinary peptide, which is a reason to expect it persists longer than one, not a measurement that it does.

The before-and-after photographs that circulate are therefore untethered to anything published. There is no expected timeline to compare them against, and no measurement anyone could take to tell an effect from its absence.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Escalation schedules used in studies

How trials stepped doses, reported as study design.

  • None. No study escalated the dose, and no dose-ranging work has been published.Editorial synthesis
    Editorial synthesis from general knowledge

Study durations

Treatment and follow-up periods as stated in each abstract.

  • Rat model rats 2024 Animal, preclinical
    Foxo4 dri administered at P4, P6, P8, and P10 led to outcomes similar to TUDCA and KYC.
    Source pmid-37874230 · quoted verbatim from the abstract
  • The mouse studies dosed in cycles over weeks and then measured tissue. No study of any length exists in a person, so no duration of use has ever been evaluated for safety.Editorial synthesis
    Editorial synthesis from general knowledge · primary document to be added to the ledger

Routes: intraperitoneal in the mouse studies

Routes of administration named in each study.

  • Rat model rats 2024 Animal, preclinical
    N -acetyl-lysyltyrosylcysteine-amide (KYC), tauroursodeoxycholic acid (TUDCA), and Foxo4 dri were administered intraperitoneally to mitigate myeloperoxidase oxidant generation, ER stress, and cellular senescence, respectively.
    Source pmid-37874230 · quoted verbatim from the abstract
  • Animal study mice 2026 Animal, preclinical
    Injection of FOXO4-DRI in both naturally aged and induced aging mice effectively suppressed aortic aging and improved aortic function.
    Source pmid-41625068 · quoted verbatim from the abstract
  • Intraperitoneal injection in every animal study, which is a route used in rodents and not in people. No study has used subcutaneous injection, the route people who buy it describe, and none has tested whether the peptide survives or distributes the same way by that route.Editorial synthesis
    Editorial synthesis from general knowledge

Weight-normalized doses, as published

Per-kilogram figures exactly as each study published them, for the species it studied.

  • 5 milligrams per kilogram intraperitoneally in mice, from the 2017 paper's methods. No per-kilogram figure has ever been established for any other species, and none has been tested in a person.Editorial synthesis
    Editorial synthesis from general knowledge · primary document to be added to the ledger

Weight-normalized figures above are reproduced exactly as each study published them, for the species it studied. Dose does not scale linearly with body mass between species: metabolic rate, clearance and receptor density differ, and regulatory guidance uses allometric, not proportional, conversion. A mg/kg figure from a rat study is a fact about that rat study and nothing else.

What people report outside the literature

Community posts describe injecting a few hundred micrograms a day in cycles of a few weeks, sometimes under the vendor name Proxofim, with before-and-after photographs and self-reported energy and skin changes. None of it is measured, and the schedule is not the one the mouse studies used. What circulates in user communities and clinic marketing, reported so a reader knows the figures and their origin. None of it has been tested in a trial, and none of it is a suggestion.

  • What circulates is a schedule, not a finding. Community posts and vendor pages describe subcutaneous injection of a few hundred micrograms a day, laddered over several weeks and repeated in cycles, sometimes under the vendor name Proxofim, with before-and-after photographs and self-reported changes in energy, skin and recovery. None of this is measured, none of it matches the mouse regimen it cites, and there is no test a person could take to check whether anything happened. It is recorded here because people search for it, and the figures are not reproduced.Editorial synthesis
    Editorial synthesis from general knowledge
Method note · shared across compounds

Reconstitution mathematics

Lyophilised peptide is supplied as a mass in a vial and dissolved in a stated volume of diluent. Two figures follow from that and nothing else:

  • Concentration = mass in vial ÷ diluent volume. A 5 mg vial in 2 mL is 2.5 mg/mL, or 2,500 mcg/mL.
  • Volume for a given mass = that mass ÷ concentration. 250 mcg at 2,500 mcg/mL is 0.1 mL. On a U-100 insulin syringe, where 1 mL is 100 units, that is 10 units.

Study doses on this page are quoted as published, in the units the authors used. Converting between mcg, mg and IU, or between a mass and a syringe volume, is arithmetic; deciding a mass is not, and this page does not do it. The reconstitution calculator performs the conversion with the formula shown.

Method note · shared across compounds

Reading a certificate of analysis

A certificate of analysis is a laboratory report on one batch. Reading it means checking four things in order.

  1. Identity. Mass spectrometry should report an observed molecular mass matching the peptide's theoretical mass within the instrument's stated tolerance. A certificate with no mass spectrometry, or one that lists only the expected value, has not confirmed identity.
  2. Purity. HPLC purity is the area of the main peak as a share of all peaks, at a stated wavelength. It says nothing about what the other peaks are, and it is not a measure of quantity.
  3. Quantity. Net peptide content, by amino acid analysis or UV, is the fraction of the vial's mass that is peptide rather than counter-ions and water. A 5 mg vial at 80% net content holds 4 mg of peptide, and every concentration figure above changes accordingly.
  4. Provenance. The batch number on the certificate should match the vial, the laboratory should be named and independent of the seller, and the test date should be recent.

This page rates no supplier and links to none. It describes how to read the document.

Method note · shared across compounds

Equipment described in studies

Published human studies of injectable peptides report the same small set of materials: single-use insulin syringes with fixed needles, most often U-100 with 29 to 31 gauge needles; bacteriostatic water or sterile water for injection as diluent, with the choice stated in the methods; alcohol swabs; and refrigerated storage of reconstituted solution. Animal studies more often report intraperitoneal or intragastric administration and state the vehicle used. Where a study in this record's ledger names its materials or vehicle, that sentence appears under storage or routes above; where it does not, nothing is assumed here.

Storage and handling

No storage or stability study for FOXO4-DRI has been published, and the ledger holds none. What is known generally is that an all-D-amino-acid peptide is more resistant to enzymatic breakdown than an ordinary one, which says nothing about how a lyophilised vial behaves on a shelf or in solution. Vendor handling instructions describe a product that no regulator has assessed.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Common mistakes in how FOXO4-DRI is discussed

  1. Reading the human-cell studies as human studies. Cartilage cells in a flask and keloid tissue in culture are human material, not people.
  2. Citing the 2017 mouse paper for a microgram schedule. The paper's regimen was milligrams per kilogram, intraperitoneally, in cycles. The two have no arithmetic relationship.
  3. Treating research-use-only as a regulatory category that permits use. It means the opposite: nothing has been assessed, and the product is not intended for human consumption.
  4. Assuming a growing publication count means progress towards approval. Most new papers use the peptide as a probe for another disease.
  5. Expecting a felt effect. Senolysis is measured in tissue. Any before-and-after impression is unverifiable, which is why the community evidence here stays in its own section.
  6. Grouping it with senolytics that have human data. Dasatinib with quercetin, fisetin and navitoclax have been through human trials. This has not. The comparison below keeps them apart, and epitalon is an example on this site of the same pattern: heavy community interest, thin human evidence.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

FOXO4-DRI beside the senolytics that have reached human trials

Senolytic approaches compared by how far they have got in people.
ApproachWhat it isHuman evidenceWhere it stands
FOXO4-DRID-retro-inverso peptide, blocks the FOXO4-p53 interactionNoneNo registered trial; sold as a research chemical
Dasatinib with quercetinAn approved leukaemia drug plus a flavonoid, given intermittentlySmall early trials in lung fibrosis, kidney disease and Alzheimer's diseaseThe most studied senolytic combination in people
FisetinA flavonoid available as a supplementTrials in older adults running and reportedOral, cheap, and the compound reviews cite when they need human data
NavitoclaxA BCL-2 family inhibitor from oncologyLater-stage trials in blood cancers, with senolytic trials proposedEffective but lowers platelets, which limits use in healthy ageing
UBX-series compoundsPurpose-built senolytics, given locallyEye injections trialled in retinal diseaseThe local-delivery answer to the selectivity problem

The pattern is worth noticing: everything with human data is either a repurposed drug or delivered locally. A systemically injected peptide that clears cells throughout the body is the hardest version of this idea to test, which is part of why it has not been. For a different class of compound aimed at protecting rather than clearing cells, see ARA-290, the other entry in this class on this site; the full list is in the compound directory.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Other compounds in its class

Same class in the registry: ARA-290. Each row shows what that compound's own record states; nothing is inferred across rows.

2 compounds in the senolytic & cytoprotective class. Each row states what that compound's own record says; nothing is inferred across rows.
CompoundTierPublicationsRCTsRecord
FOXO4-DRI Animal, preclinical 19 0 draft
ARA-290 Human clinical trial 39 3 draft

Who owns it, and why it has not moved

The peptide came out of Peter de Keizer's group at the Erasmus University Medical Center in Rotterdam, published in Cell in 2017 to considerable coverage. Cleara Biotech was founded to commercialise the work. The company remains a preclinical concern and its programme has moved towards the FOXO4-p53 interaction in general rather than this particular molecule, which is the ordinary fate of a first-generation peptide: too large, too expensive to synthesise, too awkward to deliver, and difficult to protect commercially in a form anyone can already buy.

The 2025 structural work points the same way. Having mapped how the peptide binds, one group designed a shorter successor built from ordinary L-amino acids with a redesigned charge profile, because that is easier to make and to develop. A compound whose own field is designing replacements for it is not a compound about to enter trials.

Meanwhile the literature keeps growing, because the peptide is a convenient way to ask whether senescent cells matter in a given disease. Those papers are evidence about senescence. They are not a development programme, and reading a steady stream of publications as momentum towards a medicine is the mistake this section exists to prevent.

Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.

Regulatory status: no approval, no registered trial, sold as a research chemical

Registry facts only. Jurisdiction-level status, compounding categories and sport prohibitions need their own cited documents before they appear here.

  • No approval anywhere, and no registered clinical trial. The peptide was described in 2017 by a group at the Erasmus University Medical Center in Rotterdam; Cleara Biotech was founded on that work and has since focused on the FOXO4-p53 interaction more broadly rather than on this molecule, and no first-in-human study has been registered in the nine years since. It is sold as a research chemical, often under the vendor name Proxofim, with the research-use-only label that means no regulator has assessed it and it is not intended for human consumption. It is not named on the World Anti-Doping Agency's Prohibited List; as an unapproved substance it falls under the S0 category covering drugs with no current regulatory approval.Editorial synthesis
    Editorial synthesis from general knowledge · primary document to be added to the ledger

Open questions and limitations

What is genuinely unknown, stated plainly. A missing field is not evidence that the outcome is safe, effective, or established.

  • No human has received FOXO4-DRI in a published study, and no trial is registered.
  • No pharmacokinetic study exists in any species: no half-life, no distribution, no measure of how long a dose persists.
  • Doses live in methods sections rather than abstracts, so the ledger's dose fields are empty apart from the 2017 mouse regimen, which is recorded editorially.
  • No published analysis of the purity or content of vials sold under this name, or under the vendor name Proxofim.
  • Whether clearing senescent cells systemically has a cost in wound healing or tissue repair has not been measured in any species.
  • No randomized controlled trial of FOXO4-DRI is indexed in Europe PMC.

Study limitations

  • No first-in-human study, no registered trial and no pharmacokinetic data in any species.
  • Doses are in methods sections rather than abstracts, so the ledger's dose fields are mostly empty.
  • Most papers use the peptide as a laboratory probe for a disease mechanism, not as a candidate being developed.

Questions people ask

What is Proxofim?

Proxofim is a name several research-chemical vendors use for FOXO4-DRI. It is not the brand of an approved medicine, it denotes no particular purity or manufacturer, and no regulator has assessed anything sold under it. The name appears in vendor listings and search suggestions, not in the scientific literature.

What is FOXO4-DRI?

FOXO4-DRI is a synthetic peptide designed in 2017 at the Erasmus University Medical Center to break the grip senescent cells keep on the protein p53. It is built from D-amino acids in reverse order, which is what D-retro-inverso means, so enzymes cannot easily degrade it. In mice it killed senescent cells selectively and restored fur density, fitness and kidney function in old animals. It has never been given to a person in a trial, and it is sold online under the vendor name Proxofim.

What is the half-life of FOXO4-DRI?

No published study gives one, and no abstract in this ledger states a figure. The D-retro-inverso design exists precisely to slow degradation, because a peptide of ordinary L-amino acids would be cleared quickly, but resistance to enzymes is not the same as a measured half-life. Nothing has been measured in a person at all.

Does FOXO4-DRI regrow hair?

The 2017 mouse paper reported restored fur density in old and in chemotherapy-treated mice, which is where the question comes from. Fur density in a mouse is not hair growth in a person, no trial has looked, and the mechanism proposed is the clearance of senescent cells in aged skin rather than anything acting on hair follicles.

What did FOXO4-DRI do to kidney function in mice?

The 2017 paper reported that renal function improved in fast-ageing and in naturally aged mice after the peptide was given. Senescent-cell accumulation in the kidney is one of the better-studied targets for senolytics generally, and a 2018 review in this ledger argues the same for transplanted kidneys. No human kidney has been studied.

Has FOXO4-DRI been tested in humans?

No. There is no completed, ongoing or registered human trial, nine years after the 2017 paper that designed it. The studies whose records mention humans used human cartilage cells in culture, human keloid tissue in culture, human proteins in a structural experiment, and autopsy lung tissue examined alongside a rat model. Nobody has received the peptide in a published study.

What dose was used in the studies?

The original 2017 mouse work used 5 milligrams per kilogram intraperitoneally, in cycles of three doses repeated over weeks, a figure that appears in the paper's methods rather than its abstract. The newborn rat study dosed on four days across one week without stating an amount in its abstract. No other study in the ledger states a dose, and none has been given to a person.

What are the side effects of FOXO4-DRI?

Unknown, because no person has taken it in a study. The 2017 paper reported that mice tolerated it at the doses used. That is not a safety assessment: those studies were looking for benefit. The untested concerns that follow from the mechanism are the role senescent cells play in wound healing, the fact that the peptide enters all cells and relies on what the cell depends on for its selectivity, and the unknown contents of vials sold online.

How does FOXO4-DRI work?

Senescent cells survive by using the protein FOXO4 to hold p53 in the nucleus, where it cannot start the cell-death programme. FOXO4-DRI carries the part of FOXO4 that binds p53, so it competes for the same site, releases p53 and lets the cell destroy itself. Healthy cells do not depend on that interaction, which is the basis of the selectivity claim.

What does the DRI in FOXO4-DRI mean?

D-retro-inverso. The peptide is assembled from mirror-image D-amino acids in reverse sequence, which presents a similar shape to the target while being unrecognisable to the enzymes that break down ordinary peptides. A cationic cell-penetrating sequence is attached to carry it into cells, and a 2025 structural study found that this sequence also contributes to the binding.

Is FOXO4-DRI the same as Proxofim?

Proxofim is a name research-chemical vendors use for FOXO4-DRI. It is not the brand of an approved medicine and denotes no particular purity, manufacturer or assessment. The name appears in vendor listings, not in the scientific literature.

Is FOXO4-DRI approved or legal?

It is approved nowhere and has no registered trial. It is sold as a research chemical under a research-use-only label, which means no regulator has assessed it and it is not intended for human consumption. Rules on buying and possessing research chemicals vary by country.

Did FOXO4-DRI extend lifespan in mice?

The 2017 study measured health rather than lifespan: fitness, fur density and kidney function improved in fast-ageing and naturally aged mice, and the toxicity of a chemotherapy drug was blunted. Later mouse studies measured testosterone, sperm quality, lung fibrosis, radioresistance and aortic function. A survival study of this peptide has not been published.

Why has FOXO4-DRI not reached clinical trials?

The company founded on the work has moved towards the underlying protein interaction rather than this molecule. A large all-D-amino-acid peptide is expensive to make, awkward to deliver, hard to protect commercially once it can be bought openly, and difficult to test, since senolysis has no blood-borne readout that would show a trial whether the drug worked. A 2025 group has already designed a shorter successor.

Can you measure whether FOXO4-DRI has worked?

Not outside a laboratory. Senescence is measured in tissue: p16, beta-galactosidase staining and the secreted inflammatory signature, generally from a biopsy. There is no validated blood test, which is a problem for the whole senolytic field and the reason self-experiment here produces no information.

Is FOXO4-DRI better than dasatinib and quercetin or fisetin?

There is no basis for the comparison. Dasatinib with quercetin and fisetin have both been through small human trials; FOXO4-DRI has not been given to a person. On mechanism it is more targeted, acting on one protein interaction rather than several survival pathways, but a targeting advantage shown in mice cannot be weighed against results in people.

Which species has FOXO4-DRI been studied in?

Mice in most studies, rats in the newborn lung study, and human cells in culture. There are no studies in dogs, in non-human primates or in people.

Sources

Full citations. Every claim above links to one of these by its id.

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    Cellular senescence in the aging and diseased kidney.
    pmid-29260442 · · peer-reviewed
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Reference card

Reference card · generated /compounds/foxo4-dri
Compound
FOXO4-DRI, senolytic and cytoprotective
Evidence tier
Animal, preclinical
Indexed publications
19 · 0 RCTs · 0 other clinical trials
Approval
no registered development programme found
Routes reported
intraperitoneal
Reviewed
Adam Mirando, PharmD,

Study figures are as published in each source and are not recommendations. Print or save this card with its date.

Last reviewed and what changed

Newest first. These are the record's own revision dates, and the same dates feed the sitemap.

  1. · Reviewed by Adam Mirando, PharmD, on 2026-09-28.
  2. · Citation correction: the study-by-study table credited the 2024 spermatogenesis paper to Wang and the 2023 extracellular-matrix paper to Zhang. Their first authors are Li and Liu. Both papers were already in the ledger; only the names were wrong.
  3. · Stage 0 corrected by hand: the evidence tier read observational-human although no person has received the peptide, and the one row filed as a human study is a rat model with human autopsy lungs; both fixed, and five papers the fetcher missed were added to the ledger, including the 2017 study that designed the compound. Written under the sequencing rule after research/intents/foxo4-dri.json: guide of ten sections including a table separating human material from human studies, a full study-by-species table and a dose table; mechanism, reported use and regulatory status as editorial with pending_source; misdrafted interaction and exclusion claims removed; intent-driven H1 and title.
  4. · Claims drafted extractively from 15 ledger sources by scripts/draft_claims.py: 14 claims, 10 evidence-table rows. Status researched -> draft.
  5. · Claims drafted extractively from 15 ledger sources by scripts/draft_claims.py: 18 claims, 10 evidence-table rows. Status researched -> draft.
  6. · Claims drafted extractively from 15 ledger sources by scripts/draft_claims.py: 19 claims, 10 evidence-table rows. Status researched -> draft.
  7. · Evidence fetched from Europe PMC and ChEMBL by scripts/fetch_evidence.py; claims not yet written.