FOXO4-DRI: what the senolytic studies actually administered

What is FOXO4-DRI?

The design problem it was built to solve: senescent cells stop dividing but refuse to die, and the 2017 paper that introduced this peptide identified the protein FOXO4 as the reason. In a senescent cell, FOXO4 sits in nuclear bodies alongside p53 and keeps it there. p53 held in the nucleus enforces arrest. p53 pushed out of the nucleus triggers the cell to kill itself (Baar, 2017).

What the peptide is, physically: a chain of 46 amino acids with a molecular weight of 5358.2, printed in the paper as a single lowercase string because every residue is a D-isomer rather than the L-isomer a body normally builds. Reversing the sequence and mirroring each residue is a known trick for making a peptide survive longer in blood, and the paper cites two earlier D-retro-inverso peptides that had already reached human trials as its precedent for trying it.

Two halves, one chain: the front of the sequence copies a stretch of FOXO4 itself, the part that grips p53. The tail is a positively charged run borrowed from HIV-TAT, which is what carries the whole thing across a cell membrane. A 2025 structural study using nuclear magnetic resonance found that both halves contribute to the binding, not just the FOXO4-derived front, and measured the peptide binding the first 94 residues of p53 with a dissociation constant of 400 plus or minus 280 nanomolar, about 5 times tighter than the natural FOXO4 domain manages (Bourgeois, 2025).

What the name is not: DRI is a description of the chemistry, not a brand and not a batch code. Nothing in the published record attaches a trade name to this molecule, and there is no approved product whose label could settle what a container of it holds. That leaves the same identity gap that a purity percentage on a certificate does not close.

The cell-culture numbers, and why they are a different unit

What laboratories add to a dish: a concentration, measured in micromolar, not a body weight amount. These two kinds of number look comparable on a page and are not: one describes how much peptide surrounds a cell, the other describes how much entered an animal.

• 25 micromolar is the working concentration in the original paper's human lung fibroblast experiments, and the same figure appears in a keloid scar study on fibroblasts and whole tissue held in culture (Kong, 2025) and in a study removing senescent cells from human cartilage cells expanded for transplant, over a five-day exposure (Huang, 2021).
• 20 to 50 micromolar covers the range in the radiotherapy work, which used 50 micromolar on cancer-associated fibroblasts and 20 micromolar on a lung fibroblast line, after testing across 0 to 160 micromolar (Meng, 2021).
• 13 to 215 micromolar is the full spread of half-maximal inhibitory concentrations across three fibroblast types at three timepoints in the fibrosis work (Han, 2022). Both ends of that range are the same cell type: mouse lung fibroblasts read 215 micromolar at 24 hours untreated and 13 micromolar at 72 hours after the cells were pushed toward a myofibroblast state, so the sixteenfold gap is exposure time and cell state, not one fibroblast against another.

Why that spread deserves attention: at a matched timepoint the gap between cell lines is real but far smaller, roughly fourfold at 24 hours and under twofold at 72. What moves the number by sixteenfold is how long the cells were exposed and what state they were in. The dish experiments are the only ones in this literature that varied the amount at all, and what they show is that the concentration needed depends heavily on conditions that an animal dose in milligrams per kilogram does not record.

The selectivity claim, stated precisely: the original paper reports that the peptide kills senescent cells at concentrations healthy cells tolerate, and quantifies that gap as a selectivity index rather than as a safety margin. It also reports that, in those cultures, splitting a concentration into three smaller exposures cleared more senescent cells than delivering the same concentration at once. Both findings are about cells in plastic, and neither was tested in an animal.

Has FOXO4-DRI been given to a person?

Not in any record we could find. Searching ClinicalTrials.gov through its version 2 interface on 9 August 2026 for FOXO4-DRI returned zero studies, and the broader term FOXO4 returned one study that is a lymphoma chemotherapy trial matching on an unrelated field. The World Health Organization's international registry portal, queried the same day, answered "No results were found". A query for semaglutide on both, run as a control, returned 759 studies and a page of trial records respectively, which is how we know the endpoints answer when there is something to answer with.

On approval: the openFDA drug approvals endpoint and the drug labeling endpoint both returned NOT_FOUND for FOXO4 on 9 August 2026, while the same approvals query for semaglutide returned a record. One country's database returning nothing is a boundary on our checking, not a finding about the rest of the world. A 2026 review of FOXO4 biology puts the same point in its own words, describing the peptide as having shown senolytic activity in preclinical models while remaining clinically unvalidated, and listing pharmacokinetics, delivery, long-term toxicology and the effect on p53-dependent tumor surveillance as the work still outstanding (Mateescu, 2026).

What that absence is and is not: it is not evidence the molecule failed in people, because no one has published giving it to any. It is the absence of the evidence that would answer the question either way, and it is why a page about dosage for this compound has an animal table and no human one.

Why does the mouse figure not scale to a person?

The short version: a milligram per kilogram in a mouse and a milligram per kilogram in a human are the same arithmetic and different pharmacology, and nothing in this compound's published record bridges the two.

What is missing to make that bridge: the peptide has no published pharmacokinetic study. On 9 August 2026 we searched the PubMed index for FOXO4-DRI together with pharmacokinetics, toxicology, half-life, bioavailability or maximum tolerated dose, and it returned two records, both of them reviews and neither reporting an original measurement. So there is no blood concentration curve, no clearance figure, no half-life and no established tolerated ceiling in any species, including the mouse. Every animal amount in the table above was administered by injection, and no route by mouth is reported at all.

Why a number without those measurements does not travel: the animal figure is a dose that produced an effect in one strain, on one schedule, in one laboratory's hands, with no dose-response curve behind it and no exposure measurement to anchor it. A figure with no curve underneath cannot tell anyone where its own edges are, which is exactly what a person would need to know. This is the same wall as reading an animal amount across to a human body, with less to work from than that page has.

One more difference that is easy to miss: three routes appear across the table, a vein, the abdominal cavity and the spinal fluid, and the choice between the first two was made for experimental convenience rather than for pharmacology. The original paper switched routes mid-study to match the comparison drug. The third route bypasses the bloodstream entirely, which is why its amount is a thousand times smaller and is reported in micrograms rather than per kilogram. Route is not a detail that survives translation, and a compound with no oral data has no route a person could copy anyway.

Is ES2 the same molecule?

No. ES2 is a separate peptide, designed by a different group by molecular modeling of the FOXO4 and p53 interaction, and it is frequently discussed alongside FOXO4-DRI as though the two were interchangeable (Le, 2021).

The measured difference: ES2 binds FOXO4 with a dissociation constant of 0.660 plus or minus 0.006 nanomolar and p53 with 2.3 plus or minus 0.018 nanomolar, so it prefers FOXO4 by about fourfold, and it showed senolytic activity at 8 micromolar in cells.

The amounts differ in kind, not just in size: ES2 in aged mice was given as 3 milligrams total by tail vein once a week for three weeks, in animals started at 82 weeks of age. That is a flat amount rather than an amount per kilogram, the same unit the spinal-fluid row of the table uses and a different one from every other row. Its tumor work was injected directly into the tumor rather than into the bloodstream. Anyone reading an ES2 figure as a FOXO4-DRI figure is combining two molecules, and on this evidence two molecules whose reported amounts differ by more than a thousandfold depending on which unit and route you read.

What about the claims that it restores the aging brain?

A 2026 review in a pharmacology journal is the most prominent recent publication on this peptide, and its abstract states that in aged mammalian models the peptide restores cerebral blood flow and blood-brain barrier integrity, reverses hippocampal atrophy, improves cognition, and that in Alzheimer's and tauopathy models it clears amyloid-beta and pathological tau (Alameen, 2026).

We went looking for the studies behind those sentences and did not find them. On 9 August 2026 we searched the PubMed index for FOXO4-DRI paired with brain, hippocampal, Alzheimer, cognitive, tau or blood-brain barrier, and it returns exactly 2 records: that review itself, and a vascular study of the aorta. On the same date, 9 August 2026, we searched the full text at Europe PMC for FOXO4-DRI together with Alzheimer, hippocampal or amyloid, and it returns 67 records. We read the titles and abstracts that query returned rather than all 67 papers in full, and that is the limit of the claim: among them we found no experiment giving this peptide to an animal and measuring amyloid, tau, hippocampal volume or cerebral blood flow. Some are primary brain studies, but the ones we checked clear senescent cells by another method, a genetic construct or a different senolytic drug, rather than with this peptide.

What we are and are not saying: we are not saying those experiments do not exist. A review's reference list can reach work that neither index surfaces by these queries, and the review sits behind a publisher wall we could not open, so we could not check its citations. What we can say is that the two literature searches we ran and dated did not reach a primary source for any of it, and that a reader who meets those claims in a summary should know they are a review's summary rather than a result we could trace. It is the same caution this library applies to a compound whose reputation runs well ahead of its primary literature.

Where the evidence cuts the other way

A result that points the opposite way: a 2023 paper in Circulation set out to test whether clearing senescent cells helps in pulmonary hypertension, a disease of the blood vessels in the lungs, and found that it can make it worse. Clearing those cells with a suicide gene or with the senolytic drug ABT263 raised right ventricular systolic pressure and the hypertrophy index, increased vessel remodeling, and markedly reduced the pulmonary endothelial cells lining those vessels (Born, 2023).

Where this peptide comes into it, stated separately: those pressure and remodeling figures belong to the suicide-gene and ABT263 arms, not to FOXO4-DRI, and merging the two would misreport the paper. The peptide appears in its own arm: in mice engineered to overexpress the serotonin transporter, animals given either ABT263 or FOXO4-DRI showed pulmonary hemodynamic alterations and the same loss of pulmonary endothelial cells against their relevant controls.

Why it belongs on a page about amounts: because among the studies we retrieved it is the only one in which this peptide made a disease worse rather than better, and it used the same molecule as everything in the table. The paper's own conclusion is that eliminating senescent endothelial cells may worsen pulmonary blood flow, and that this invites caution about strategies aimed at controlling senescence generally. A 2026 review of the same field describes preclinical senolytic results in this disease as conflicting and argues for short, intermittent, stage-aware regimens rather than broad clearance (Hirsch, 2026).

One correction in the record: the 2022 fibrosis paper carries a published corrigendum. Its authors found that two flow cytometry panels in one figure had been duplicated, with the scatter plot from one treatment group placed in another, and state that the article's conclusion is unchanged. We print it because a reader checking this literature should meet the correction at the same time as the paper (Correction, 2024).

Where the evidence runs out

Six limits on what this record supports:

• One dosing decision, copied six times, and two that were not. Six of the nine experiments use the 2017 paper's figure and cite it for the choice. Independent groups replicating an effect is evidence; independent groups reusing a number is not. The two experiments that did choose independently landed on a different amount and a different unit, which is the clearest sign in this literature that the figure was never settled by measurement.
• No dose-response curve in any animal. We found no study that gave two different amounts to animals and compared them. Without that there is no lowest effective amount, no ceiling, and no shape to the relationship between amount and effect.
• No pharmacokinetics anywhere. No published measurement of blood levels, clearance or half-life in any species, which is the measurement that would let anyone reason about exposure rather than about injected quantity.
• No toxicology package in the literature. Every safety statement available is a negative finding reported inside a study designed to test whether the peptide works, most of them from the originating laboratory. Nothing we retrieved was designed to look for harm.
• The mechanism cuts both ways by design. The peptide works by releasing p53, which is the cell's main tumor suppressor and also the switch it uses to arrest damaged cells. The 2026 redox review names explicit assessment of p53-dependent tumor surveillance as outstanding work (Mateescu, 2026), and that concern is intrinsic to how the molecule functions rather than incidental to it.
• Anti-doping status not settled by a name search. We read the 2026 Prohibited List from the copy published by the International Testing Agency and searched it for FOXO4, senolytic and retro-inverso, with zero occurrences of any of them; BPC-157, which the same document does name, is the control showing the search works. That is not a clearance. The list's first class covers any pharmacological substance it does not address later that no government health authority has approved for human therapeutic use, wording that reaches molecules the document never names (WADA, 2026).

Nine animal experiments across eight papers, every one of them an injection into a rodent, plus two further animal papers whose amounts we could not reach, in the searches set out below.

How this page is sourced

Which document carries which claim: the molecule's design, sequence, weight and original animal schedule come from the 2017 primary paper; the eight other animal regimens from seven later primary papers, one of them taken from a 2026 review because the study itself is paywalled, with two further animal papers cited whose amounts we could not reach; the cell-culture concentrations from four of those plus two in vitro studies; the binding measurements from a 2025 structural paper and a 2021 peptide-design paper; the counter-evidence from a 2023 cardiovascular paper and a 2026 review of that field; the correction from the publisher's own corrigendum; the clinical status from two reviews plus registry, regulator and anti-doping queries we ran and dated; and the absence claims from literature searches whose exact queries are printed below.

Twenty-three sources: seventeen journal articles carrying both a linked DOI and a PubMed ID, one published corrigendum carrying both as well, two trial registry queries, one regulator database query, one anti-doping list read from a copy published elsewhere, and one record of the literature searches that produced every count here. Seven of those eighteen identifiers answered an automated request to their publisher with HTTP 403, which is a bot wall rather than a dead link, and all eighteen resolved to matching metadata at Crossref, the authority we used for those seven.

How the literature was counted, and what the counts do and do not mean: on 9 August 2026 we searched the PubMed E-utilities interface for the phrase "FOXO4-DRI", which PubMed translates to "FOXO4-DRI"[All Fields], and it returns 19 records. We read the title and abstract of every one. Twelve concern this peptide directly; the rest name it in passing inside senescence reviews or in primary work on something else. On the same date we searched the same interface for "FOXO4-D-Retro-Inverso"[All Fields], which returns 2. We then searched the full-text index at Europe PMC for that first phrase, again on 9 August 2026, and it returns 297 records.

Why the gap between 19 and 297 is the important number: it is the difference between a name appearing in an abstract and a name appearing anywhere in a paper. It also caught the omission that would have damaged this page most. The 2017 paper that created this peptide does not contain the string FOXO4-DRI in its own abstract, which calls it a FOXO4 peptide, so the phrase search that returns nineteen records does not return the founding paper. We reached it through the full-text index and through a commentary on it, and a page built from the abstract search alone would have been missing the only study that reports the sequence and the original schedule. An index answers for its own contents, and a query cannot see past them.

What we could not retrieve, and one thing we wrongly thought we could not: three of the papers cited here are not open access, so for Liu 2023, Li 2024 and Born 2023 we worked from abstracts, PubMed records and, for Born, a later review's tabulation, rather than from their own methods sections. An earlier draft of this page also reported the newborn rat study's amount as unreachable. That was our error, not the publisher's: the automated interface we queried returns only an abstract for that record, while the same article is free in full at its PubMed Central address, where the amount is stated plainly. One tool answering thin is not a document being unavailable, and the figure that draft omitted turned out to be twice the one the rest of the page reports. The 2026 review that makes the brain claims is genuinely behind a wall, which is why we report our own searches for its underlying studies instead of assessing its reference list.

The standard: the checks a citation passes before it reaches a page, and the review a page passes before it ships, are set out on the methodology page. On a compound with nine animal experiments and no human data, that standard is most of what separates this page from a summary of a summary.

Last reviewed: 9 August 2026.

1. 1

   Baar MP, Brandt RMC, Putavet DA, et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell. 2017;169(1):132-147.e16. doi:10.1016/j.cell.2017.02.031. PMID 28340339. The primary source for the sequence, the molecular weight, the original animal schedule, the cell-culture concentration, the platelet result and the route switch. Full text read at PMC5556182.

2. 2

   Zhang C, Xie Y, Chen H, et al. FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging (Albany NY). 2020;12(2):1272-1284. doi:10.18632/aging.102682. PMID 31959736. Source of the 5mg per kg schedule in 20 to 24 month old mice and of the testosterone and organ weight results. The publisher's host returned HTTP 403 to an automated request for the DOI; metadata verified at Crossref.

3. 3

   Meng J, Li Y, Wan C, et al. Targeting senescence-like fibroblasts radiosensitizes non-small cell lung cancer and reduces radiation-induced pulmonary fibrosis. JCI Insight. 2021;6(23):e146334. doi:10.1172/jci.insight.146334. PMID 34877934. Source of the weekly two-cycle schedule and of the 20, 50 and 0 to 160 micromolar culture figures.

4. 4

   Han X, Yuan T, Zhang J, et al. FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway. J Cell Mol Med. 2022;26(11):3269-3280. doi:10.1111/jcmm.17333. PMID 35510614. Source of the day 14, 16 and 18 schedule, of the comparison with the approved fibrosis drug, and of the 13 to 215 micromolar spread. Read with its corrigendum, reference 5. The publisher's host returned HTTP 403 to an automated request; metadata verified at Crossref.

5. 5

   Correction to "FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway". J Cell Mol Med. 2024;28(16):e18502. doi:10.1111/jcmm.18502. PMID 39166551. A published corrigendum, not a retraction. It corrects duplicated flow cytometry panels in one figure of reference 4 and states the conclusion is unchanged. The publisher's host returned HTTP 403 to an automated request; metadata verified at Crossref. Full text read at PMC11337111.

6. 6

   Hu Z, Li F, Hu C, et al. FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway. Front Bioeng Biotechnol. 2026;13:1729166. doi:10.3389/fbioe.2025.1729166. PMID 41625068. Source of the every-two-days month-long schedule in 17 month old mice. PubMed dates this record 2025 by volume year; the publisher registered it as published on 15 January 2026, which is the year printed here.

7. 7

   Jing X, Jia S, Teng M, et al. Cellular senescence contributes to the progression of hyperoxic bronchopulmonary dysplasia. Am J Respir Cell Mol Biol. 2024;70(2):94-109. doi:10.1165/rcmb.2023-0038OC. PMID 37874230. The only non-mouse animal study on this list, and the source of the 10mg per kg figure. Its Animal Treatment section reads "Foxo4 dri 10 mg/kg was administered at P4, P6, P8, and P10". Read in free full text at PMC12042139, HTTP 200. The publisher's own host returned HTTP 403 to an automated request, and the E-utilities interface returns only an abstract for this record, which is what an earlier draft of this page wrongly read as the full text being unavailable; metadata verified at Crossref.

8. 8

   Liu Y, Hou Q, Wang R, Liu Y, Cheng Z. FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(10):2393-2403. doi:10.1007/s00210-023-02452-2. PMID 37074394. A second independent mouse fibrosis study. Not open access, so it contributes to the count of animal work on this page and not to the table: we could not read its amount or schedule.

9. 9

   Li Y, Zhang C, Cheng H, et al. FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells. Exp Gerontol. 2024;195:112522. doi:10.1016/j.exger.2024.112522. PMID 39025385. The follow-up to reference 2 from an overlapping group. Not open access, so it is counted as animal work without a retrievable amount.

10. 10

    Kong YX, Li ZS, Liu YB, et al. FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation. Commun Biol. 2025;8(1):299. doi:10.1038/s42003-025-07738-0. PMID 39994346. Source of one 25 micromolar culture figure. Fibroblasts and tissue held in culture, no animal was dosed.

11. 11

    Huang Y, He Y, Makarcyzk MJ, Lin H. Senolytic peptide FOXO4-DRI selectively removes senescent cells from in vitro expanded human chondrocytes. Front Bioeng Biotechnol. 2021;9:677576. doi:10.3389/fbioe.2021.677576. PMID 33996787. Source of the 25 micromolar over five days figure in human cartilage cells, and of the finding that its benefit for cartilage formation was not established.

12. 12

    Born E, Lipskaia L, Breau M, et al. Eliminating senescent cells can promote pulmonary hypertension development and progression. Circulation. 2023;147(8):650-666. doi:10.1161/CIRCULATIONAHA.122.058794. PMID 36515093. The counter-evidence, and the only animal result here in which the intervention worsened the disease. The publisher's host returned HTTP 403 to an automated request; metadata verified at Crossref.

13. 13

    Hirsch K, Horn AG, Donato AJ, Schulze KM. The right time, the right cell: the potential for precision senotherapy in pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. 2026;330(6):L661-L669. doi:10.1152/ajplung.00104.2026. PMID 42030209. A review, cited for its characterization of the preclinical senolytic results in this disease as conflicting, for its argument for short intermittent regimens, and for the Born regimen in the table above: its Table 1 tabulates that study as FOXO4-DRI at 5 mg/kg, three times per week, intraperitoneally, across days 0 to 21. We use the review for that row because reference 12 itself is paywalled, and the caption says so rather than presenting it as read from the source. Read in free full text at PMC13202487. The publisher's host returned HTTP 403 to an automated request for the DOI; metadata verified at Crossref.

14. 14

    Bourgeois B, Spreitzer E, Platero-Rochart D, et al. The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI. Nat Commun. 2025;16(1):5672. doi:10.1038/s41467-025-60844-9. PMID 40593617. Source of the 400 plus or minus 280 nanomolar dissociation constant and of the finding that the cell-penetrating tail contributes to binding.

15. 15

    Le HH, Cinaroglu SS, Manalo EC, et al. Molecular modelling of the FOXO4-TP53 interaction to design senolytic peptides for the elimination of senescent cancer cells. EBioMedicine. 2021;73:103646. doi:10.1016/j.ebiom.2021.103646. PMID 34689087. The ES2 paper. Source of both dissociation constants, the 8 micromolar culture figure, and the 3mg weekly tail vein schedule in 82 week old mice. A different molecule from the subject of this page.

16. 16

    Alameen AAM, Al-Kuraishy HM, Fawzy MN, Batiha GE. Targeting the FOXO4-p53 axis by retro-inverso peptide senolytic agents: a pharmacological strategy to mitigate brain aging and cognitive decline. Naunyn Schmiedebergs Arch Pharmacol. 2026;399(10):14659-14676. doi:10.1007/s00210-026-05309-6. PMID 42024235. A review, and the source of the brain claims this page reports as a review's summary rather than as a traced result. Its DOI resolves to the publisher, HTTP 200, but the full text is not open, so we could not read its reference list.

17. 17

    Mateescu DM, Gavrilescu DM, Marinescu AR, et al. FOXO4 as a redox-sensitive regulator of antioxidant defense and cellular senescence: cysteine-based signaling, p53 interaction, and therapeutic targeting. Antioxidants (Basel). 2026;15(7):842. doi:10.3390/antiox15070842. PMID 42510573. A review, cited for its statement that the peptide is not clinically validated and for its list of outstanding work including tumor surveillance. The publisher's host returned HTTP 403 to an automated request; metadata verified at Crossref.

18. 18

    ClinicalTrials.gov, U.S. National Library of Medicine. Registry queried 9 August 2026 through the version 2 API, query term FOXO4-DRI, returning a total count of 0, and query term FOXO4, returning 1 study which is an unrelated lymphoma chemotherapy trial. clinicaltrials.gov, FOXO4-DRI query. The same endpoint queried for semaglutide the same day returned 759 studies, which is the control showing it answers when there is something to find.

19. 19

    World Health Organization, International Clinical Trials Registry Platform. Search portal queried 9 August 2026 for FOXO4-DRI, returning a page reading "No results were found". trialsearch.who.int, FOXO4-DRI query. Run as a control on the same date, the identical portal answered a semaglutide query with a list of registered trials, so the empty result above is a real absence rather than a portal that had stopped responding.

20. 20

    U.S. Food and Drug Administration, openFDA. Drugs@FDA endpoint queried on generic name foxo4 and drug labeling endpoint queried on foxo4, both on 9 August 2026, both returning HTTP 404 with the body NOT_FOUND. api.fda.gov, Drugs@FDA query. The same query run for semaglutide returned HTTP 200 with a record, which is the control showing the endpoint answers when there is something to find.

21. 21

    World Anti-Doping Agency. Prohibited List 2026, World Anti-Doping Code International Standard, in effect 1 January 2026. Read 9 August 2026 from the copy published by the International Testing Agency, HTTP 200. ita.sport, 2026 Prohibited List. Searched for FOXO4, senolytic and retro-inverso, with zero occurrences of any of them. The same search run for BPC-157, which the document does name in class S0, returns hits, so the search itself works. Source of this page's paraphrase of the scope of class S0, which the page renders in its own words rather than as a quotation.

22. 22

    Literature searches run 9 August 2026, with the search terms printed here so every count on this page can be reproduced. PubMed E-utilities was searched for these terms on 9 August 2026: "FOXO4-DRI"[All Fields], 19 records; "FOXO4-D-Retro-Inverso"[All Fields], 2 records; "FOXO4-DRI" AND (brain OR hippocamp* OR Alzheimer* OR cognit* OR tau OR "blood-brain barrier"), 2 records; "FOXO4-DRI" AND (pharmacokinetic* OR toxicolog* OR "half-life" OR bioavailab* OR "maximum tolerated dose"), 2 records, both of them reviews. eutils.ncbi.nlm.nih.gov, FOXO4-DRI query. The Europe PMC REST interface was searched for these terms on 9 August 2026: "FOXO4-DRI", 297 records; "FOXO4-DRI" AND (Alzheimer OR hippocampal OR amyloid), 67 records. ebi.ac.uk, Europe PMC query. Each figure is what that query returned on that date, and not a claim to have seen everything published.

23. 23

    Muralidharan A, Sotocinal SG, Yousefpour N, et al. Long-term male-specific chronic pain via telomere- and p53-mediated spinal cord cellular senescence. J Clin Invest. 2022;132(8):e151817. doi:10.1172/JCI151817. PMID 35426375. Source of the only amount on this page that is not scaled to body weight, and of the only third route: "daily intrathecal injections of FOXO4 (forkhead box protein O4)-DRI (D-retro inverso) peptide (10 µg in 5 µL saline)", given once daily for five days. Read in free full text at PMC9012275. This paper sits inside the 297-record full-text set below but outside the 19-record abstract set, because its abstract calls the agent a p53-specific senolytic peptide and never names it.

Related pages

Around this page: four neighboring pages on thin evidence, on animal amounts, and on what a lab result covers.

• PE 22-28 explained: another compound whose entire record rests on one paper from one laboratory, and what that does to a dose question.
• MOTS-c guide: the animal-to-human problem again, on a peptide with more human data behind it than this one.
• Cardarine (GW501516) explained: a compound whose development stopped while its retail life carried on, with a much heavier document trail.
• What a lyophilized peptide is: what freeze-drying does to a peptide, and what the powder left behind does and does not tell you.

Next in the series: one compound gets its methods sections read end to end each week, and the result goes out in The Decadewise briefing.