Peptides / Longevity and mitochondria

Synthetic analog · 46 amino acids · 5,358.2 Da

FOXO4-DRI

Not approvedBanned in sport

FOXO4-DRI is a synthetic peptide made of D-amino acids that stops FOXO4 from binding p53, and it kills aging (senescent) cells in cell and mouse studies. It is not approved and is banned in sport as an unapproved substance. PepBank shows 39 results on FOXO4-DRI from animal and lab studies. No study in people has reported results yet. Data as of 2026-10-30.

Also known as FOXO4 DRI, FOXO4 D-Retro-Inverso peptide, FOXO4-D-Retro-Inverso, FOXO4-p53 interfering peptide, EX-A7431, Proxofim

First 40 of 46 amino acids2 changed amino acids

Evidence level: Animal and lab studies onlyNo study in people has results. ClinicalTrials.gov lists no trial.

Results in people

0% of 39 results

Results in animals

38% of 39 results

Results in lab cells

62% of 39 results

From computer models

0% of 39 results

Overview

FOXO4-DRI at a glance

What it is	Synthetic analog, 46 amino acids
Approval	Not approved for any use
In sport	Banned in sport (WADA S0)
Studies	11 studies with results. 10 of them gave FOXO4-DRI, with 39 results. 15 in animals24 in lab cells
Clinical trials	None registered
Community use	Clearing senescent cells in healthy adults (general anti-ageing, short course); Fading of age spots and rough skin patches (reported by one poster); Single-person self-experiments with before and after tests (blood work, blood pressure, DNA methylation)

The science

What is FOXO4-DRI?

FOXO4-DRI is a synthetic 46-residue peptide built from D-amino acids. It blocks the binding of FOXO4 to p53 and kills senescent cells in cell and mouse studies. It is not an approved medicine.

Amino acids in one chain

FOXO4-DRI structure and chemistry

The key facts about the molecule. Long codes are in the closed section below.

Sequence, 46 amino acidsFrom the first amino acid to the last

L1TL+R+K5−EPAS−E10IAQSI15L−EAYS20QNGWA25N+R+RSG30G+K+RPP35P+R+R+RQ40+R+R+K+K+R45G

Darker means more water-repelling+ and − show charge in the bodyOutlined: changed amino acid

Structure

FOXO4-DRI is a synthetic analog of 46 amino acids, with no ring, 2 changed amino acids.

Formula

C₂₂₈H₃₈₈N₈₆O₆₄

Molecular weight

5,358.2 g/mol

CAS number

2460055-10-9

Targets

Forkhead box protein O4 (FOXO4) (gene FOXO4): disrupts the FOXO4-p53 interaction (competes with FOXO4 for p53)Evidence: primary literatureCellular tumor antigen p53 (transactivation domain TAD2) (gene TP53): binds p53 and displaces FOXO4; causes p53 nuclear exclusion and apoptosis in senescent cellsEvidence: primary literature

Development

Academic origin: the group of Peter L. J. de Keizer (Baar et al., Cell 2017). Commercial: Cleara Biotech, a company formed to commercialise the FOXO4-DRI work (Fight Aging!, 2026-02; Lifespan.io roadmap entry). Highest phase: preclinical.

Identifiers

PubChem 167312269

Full sequence, SMILES and InChIKey

Three-letter 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

InChIKey
WVZCDZFJLXBWHG-XXZPGMBKSA-N

SMILES
CC[C@@H](C)[C@H](C(=O)N[C@H](C)C(=O)N[C@H](CCC(=O)N)C(=O)N[C@H](CO)C(=O)N[C@H]([C@H](C)CC)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCC(=O)O)C(=O)N[C@H](C)C(=O)N[C@H](CC1=CC=C(C=C1)O)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(=O)N)C(=O)N[C@H](CC(=O)N)C(=O)NCC(=O)N[C@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@H](C)C(=O)N[C@H](CC(=O)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CO)C(=O)NCC(=O)NCC(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCNC(=N)N)C(=O)N4CCC[C@@H]4C(=O)N5CCC[C@@H]5C(=O)N6CCC[C@@H]6C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCC(=O)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCNC(=N)N)C(=O)NCC(=O)O)NC(=O)[C@@H](CCC(=O)O)NC(=O)[C@@H](CO)NC(=O)[C@@H](C)NC(=O)[C@H]7CCCN7C(=O)[C@@H](CCC(=O)O)NC(=O)[C@@H](CCCCN)NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H]([C@H](C)O)NC(=O)[C@@H](CC(C)C)N

See charge, composition and 3D structure on the Scientific page

The evidence

What FOXO4-DRI studies show

Results grouped by what the studies measured. Each card shows where its results come from.

Animal and lab studies onlyNo study in people has results. ClinicalTrials.gov lists no trial.

Cells, genes and aging

17 results · 5 animal · 12 lab

In rat pups with lung injury, Foxo4‑dri had effects similar to two other drugs that reduced cell aging in the lungs. American journal of respiratory cell and molecular biology, 2024

Top results

In rat pups with lung injury, Foxo4‑dri had effects similar to two other drugs that reduced cell aging in the lungs. (American journal of respiratory cell and molecular biology, 2024)
In mice, FOXO4‑DRI injection reduced signs of aging in the aorta. (Frontiers in bioengineering and biotechnology, 2025)
In aged mice, FOXO4‑DRI improved conditions inside the testes. (Aging, 2020)

Lungs and breathing

5 results · 4 animal · 1 lab

In animals, FOXO4‑DRI eased lung scarring caused by radiation. JCI insight, 2021

Top results

In animals, FOXO4‑DRI eased lung scarring caused by radiation. (JCI insight, 2021)
In rat pups with lung injury, Foxo4‑dri had effects similar to two other drugs that improved lung air sac structure. (American journal of respiratory cell and molecular biology, 2024)
In mice with lung scarring, FOXO4‑DRI treatment gave milder lung damage than no treatment. (Naunyn-Schmiedeberg's archives of pharmacology, 2023)

Sex hormones and fertility

4 results · 3 animal · 1 lab

In aged mice, FOXO4‑DRI treatment improved sperm quality. Experimental gerontology, 2024

Top results

In aged mice, FOXO4‑DRI treatment improved sperm quality. (Experimental gerontology, 2024)
In aged mice, FOXO4‑DRI eased the age-related drop in testosterone release. (Aging, 2020)
In aged mice, FOXO4‑DRI treatment improved sperm production. (Experimental gerontology, 2024)

Heart and blood vessels

3 results · 2 animal · 1 lab

In mice, FOXO4‑DRI injection improved how well the aorta worked. Frontiers in bioengineering and biotechnology, 2025

Top results

In mice, FOXO4‑DRI injection improved how well the aorta worked. (Frontiers in bioengineering and biotechnology, 2025)
In mice prone to lung blood pressure problems, FOXO4‑DRI was linked to changes in lung blood flow pressure compared with controls. (Circulation, 2023)
In cells, FOXO4‑DRI improved the function of blood vessel lining cells. (Frontiers in bioengineering and biotechnology, 2025)

Cancer

2 results · 1 animal · 1 lab

In animals, FOXO4‑DRI made lung cancer more sensitive to radiation. JCI insight, 2021

Top results

In animals, FOXO4‑DRI made lung cancer more sensitive to radiation. (JCI insight, 2021)
In cells, FOXO4‑DRI made lung cancer cells more sensitive to radiation. (JCI insight, 2021)

Bones and joints

1 result · 1 lab

In lab tests, FOXO4‑DRI pre-treatment did not improve the ability of aged cartilage cells to form cartilage. Frontiers in bioengineering and biotechnology, 2021

Top results

In lab tests, FOXO4‑DRI pre-treatment did not improve the ability of aged cartilage cells to form cartilage. (Frontiers in bioengineering and biotechnology, 2021)

All 11 FOXO4-DRI studies by area Open the Scientific page

Key FOXO4-DRI studies

Studies in people come first, then studies in animals and in the lab.

Animals
Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression
Born et al. 2023 · Circulation · cited by 136
2 results
Animals
Targeting senescence-like fibroblasts radiosensitizes non-small cell lung cancer and reduces radiation-induced pulmonary fibrosis
Meng et al. 2021 · JCI insight · cited by 112
4 results
Animals
FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice
Zhang et al. 2020 · Aging · cited by 85
4 results
Animals
Cellular Senescence Contributes to the Progression of Hyperoxic Bronchopulmonary Dysplasia
Jing et al. 2024 · American journal of respiratory cell and molecular biology · cited by 32
3 results
Animals
FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells
Li et al. 2024 · Experimental gerontology · cited by 11
5 results

All 11 FOXO4-DRI studies

FOXO4-DRI clinical trials

ClinicalTrials.gov lists no trial of FOXO4-DRI. A trial under another name may exist.

Status and safety

Is FOXO4-DRI approved?

FDA

United States

Not approved

No approved medicine contains it.

EMA

European Union

Not approved

No approved medicine contains it.

WADA

Sport

Banned

On the 2026 Prohibited List, section S0.

No. Not approved for any use. Preclinical research only. No clinical trial phase found. The FDA, the EMA and the other sources we use show no approval (as of 13 Oct 2026). Banned in sport (WADA S0).

Laws and labels change, so check the regulator for the current status.

FOXO4-DRI side effects and safety

PepBank has no safety result from studies of FOXO4-DRI yet. That does not mean FOXO4-DRI is safe.

From the community

How people use it

What people report online. It comes from forums and guides, not from studies.

Community-reported. Not tested in trials.

Sources report that a few people inject FOXO4-DRI as a one-day test or a short course of 3 injections to clear senescent cells. One poster reports faded age spots. Reported amounts range from 3 mg per dose to 40 mg in one day. There are no human trials, and the reports are single-person accounts.

Reported routines and cautions

What people use it for

Clearing senescent cells in healthy adults (general anti-ageing, short course)S2 S4S5
Fading of age spots and rough skin patches (reported by one poster)S3 S4
Single-person self-experiments with before and after tests (blood work, blood pressure, DNA methylation)S2 S4

Reported regimens

Regimens that community sources report for FOXO4-DRI. Community-reported, not tested in trials.
Context	Route	Amount	How often	How long	Agreement	Sources
One-day self-test, reported in 2020	subcutaneous injectionThe poster dissolved the powder in 1 ml of water per injection: first a 5 mg dose in acetic acid injection water, then 5 mg, 10 mg and 20 mg in bacteriostatic water.	40 mg per day	once (all injections on one day)	1 day	single source	S1
Short course by one poster, reported in 2026 at 12 days and at 30 days after the last dose	Not statedThe posts mention injections and injection-site pain but do not name the route.	28 mg per dose	q48h (a thread member reads this as every 48 hours)	3 doses	single source (the same poster in two threads; a different member of the thread guesses the meaning of q48h)	S3 S4
Low-dose short courses mentioned in replies to the R2 thread, 2026	Not statedThe replies do not name the route.	3 mg per dose	every other day	one poster: 5 days per cycle; another poster: one cycle done, a second planned	sources differ: both replies mention 3 mg every other day, but the totals are 300 mg (second-hand, and the poster's own dose is not stated) and 9 mg. Both are in one thread and are not independent.	S4
Proposed plan for a single-person trial (2018 guide on Longecity). It is a plan, not a report of use.	subcutaneous or intramuscular injectionThe guide scales the mouse dose to a human dose given by intravenous injection. It then suggests subcutaneous or intramuscular injection for a self-experimenter, at the same dose.	25 mg per dose	three doses on alternate days	3 doses (the guide's timeline puts the doses on days 12, 14 and 16 after baseline tests)	single source	S2
Protocol summary on a community wiki that carries vendor-price links (affiliate). It reports no use by a person and gives no source for its numbers.	subcutaneous injection	3 to 25 mg per dose	every other day	short cycles of 3 to 6 doses, repeated 1 to 3 times per year	single source (affiliate wiki with no cited report of use); its range 3 to 25 mg per injection does not include the 28 mg of R2 or the 40 mg of R1	S5

Reported side effects

injection-site pain, from a minute after injection and lasting hours to a dayS1 S3
minor swelling at the injection site for a dayS1
intermittent headaches and mild stomachaches during treatment and early recoveryS3
strong tiredness at 3 mg every other day (one poster)S4

Reported benefits (claims, not shown in trials)

fading of dark age spots on the hands (more than half in one account, 75 to 90 percent in a second post by the same person) and loss of rough raised skin patchesS3 S4

Cautions

A 2018 guide states that there was no human data for FOXO4-DRI at the time of writing and that anecdotal reports should be ignored, because few people check that they obtained the right compound or check their own biochemistry.S2
A 2026 news post says people can buy the peptide from sellers for personal use and that no useful data will come from this use. It describes the company behind the work as still preclinical.S6
All reports here are single-person accounts without controls. The poster in R1 reports no effect at 40 mg and the poster in R2 reports inconclusive blood tests, so the benefit claims are not shown to come from the peptide.S1 S4

Status notes

FDA: FOXO4-DRI has no approval and is not named on the FDA 503A bulk drug substances list (updated 2026-05-14).S8
WADA: not named on the 2026 or 2027 Prohibited List. By WADA's S0 rule for substances with no approval for human use, it falls under S0 and is prohibited at all times. This is a reading of the rule, not a WADA statement about this peptide.S7
Research status: no registered human trial was found on 2026-10-13. The developer company is described as preclinical.S6

Community sources

S1Anyone had results with FOXO4-DRI? (Longecity, posts of 2020-09-26 to 2020-10-11) (opens in a new tab)longecity.org
S2How to Plan and Carry Out a Simple Self-Experiment, a Single Person Trial of Senolytic Peptide FOXO4-DRI (Longecity, 2018-03-05) (opens in a new tab)longecity.org
S3FOXO4-DRI: notes from 12 days past 3x 28mg q48h FOXO4-DRI (Rapamycin Longevity News forum, 2026-08-30; plain-text copy of thread 26360) (opens in a new tab)rapamycin.news
S4My Results after FOXO4-DRI 3x 28mg q48h (Rapamycin Longevity News forum, 2026-09-27 to 2026-10-04; plain-text copy of thread 26797) (opens in a new tab)rapamycin.news
S5FOXO4-DRI (Peptide Protocol Wiki)peptideprotocolwiki.comcarries seller links, not linked
S6People Are Still Working on the Senolytic Peptide FOXO4-DRI (Fight Aging!, 2026-02) (opens in a new tab)fightaging.org
S7WADA 2027 Prohibited List (S0 Non-approved substances; the 2026 List has the same S0 rule) (opens in a new tab)wada-ama.org
S8FDA: Bulk drug substances nominated for use in compounding under section 503A (updated 2026-05-14) (opens in a new tab)fda.gov

Gaps

No Reddit, ThinkSteroids, Meso-Rx or Elite Fitness thread with a quotable FOXO4-DRI amount was found. The Longecity 'group buy' thread (topic 95267) was not read. R1 to R4 each come from one thread or one person, so there is no independent agreement on any amount. R2 and R3 name no route. Amounts range from 3 mg to 40 mg per injection or session and no source gives a rationale tied to human data. S2 (2018) is a plan, not a report. A thread member of S4 posted a text that looks machine-written; it was not used. S6 and S7 and S8 are cited for status only and have no regimen quotes. Longecity pages carry a general site sponsor banner (not seller rankings in the thread), so S1 and S2 are not marked affiliate. S3 and S4 are cited by their plain-text '/raw/' address because the normal Discourse page keeps the post text inside a noscript block that the quote checker removes; the thread addresses are https://www.rapamycin.news/t/foxo4-dri-notes-from-12-days-past-3x-28mg-q48h-foxo4-dri/26360 and https://www.rapamycin.news/t/my-results-after-foxo4-dri-3x-28mg-q48h/26797. Regulatory pages S7 and S8 are PDFs: the quote checker was not used on them. Seller research pages were seen but not used as sources. Checker, 2026-10-13: S3 and S4 /raw/ addresses were compared with the thread pages (Discourse JSON for topics 26360 and 26797). Title, first poster (researcher6076) and first-post text are the same, and neither address is a vendor page. Thread 26360 also holds a site-admin post with an AI-written review. It was not used. R5 (S5) is an affiliate wiki with no cited report of use, kept and flagged. The Cleara Biotech candidates are not FOXO4-DRI and are not used here.

Questions and more

Ask a question about FOXO4-DRI

The answer links to every study it uses.

What does the evidence say about FOXO4-DRI?Is FOXO4-DRI tested in people?Compare with AICAR (acadesine)Compare with Elamipretide (SS-31)

Sources

Database: PepBank data for FOXO4-DRI (data version 308560)
Regulator: FDA status record
Regulator: EMA status record
Regulator: WADA status record
Community: community sources (forums and guides), as summarized in the PepBank community file

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

PepBank is a research reference. Talk to a doctor before you use any peptide.

Ask your AI about FOXO4-DRI

Curo is a peptide shop. PepBank and Curo have the same owner. See the Curo catalog (opens in a new tab).

FOXO4-DRI

Not approvedBanned in sport

Also known as FOXO4 DRI, FOXO4 D-Retro-Inverso peptide, FOXO4-D-Retro-Inverso, FOXO4-p53 interfering peptide, EX-A7431, Proxofim

What it is

Synthetic analog, 46 amino acids

Approval

Not approved for any use

In sport

Banned in sport (WADA S0)

Studies

11 studies with results. 10 of them gave FOXO4-DRI, with 39 results.
15 in animals24 in lab cells

Clinical trials

None registered

Community use

Clearing senescent cells in healthy adults (general anti-ageing, short course); Fading of age spots and rough skin patches (reported by one poster); Single-person self-experiments with before and after tests (blood work, blood pressure, DNA methylation)

Context

Route

Amount

How often

How long

Agreement

Sources

One-day self-test, reported in 2020

subcutaneous injectionThe poster dissolved the powder in 1 ml of water per injection: first a 5 mg dose in acetic acid injection water, then 5 mg, 10 mg and 20 mg in bacteriostatic water.

40 mg per day

once (all injections on one day)

1 day

single source

Short course by one poster, reported in 2026 at 12 days and at 30 days after the last dose

Not statedThe posts mention injections and injection-site pain but do not name the route.

28 mg per dose

q48h (a thread member reads this as every 48 hours)

3 doses

single source (the same poster in two threads; a different member of the thread guesses the meaning of q48h)

S3 S4

Low-dose short courses mentioned in replies to the R2 thread, 2026

Not statedThe replies do not name the route.

3 mg per dose

every other day

one poster: 5 days per cycle; another poster: one cycle done, a second planned

sources differ: both replies mention 3 mg every other day, but the totals are 300 mg (second-hand, and the poster's own dose is not stated) and 9 mg. Both are in one thread and are not independent.

Proposed plan for a single-person trial (2018 guide on Longecity). It is a plan, not a report of use.

subcutaneous or intramuscular injectionThe guide scales the mouse dose to a human dose given by intravenous injection. It then suggests subcutaneous or intramuscular injection for a self-experimenter, at the same dose.

25 mg per dose

three doses on alternate days

3 doses (the guide's timeline puts the doses on days 12, 14 and 16 after baseline tests)

single source

Protocol summary on a community wiki that carries vendor-price links (affiliate). It reports no use by a person and gives no source for its numbers.

subcutaneous injection

3 to 25 mg per dose

every other day

short cycles of 3 to 6 doses, repeated 1 to 3 times per year

single source (affiliate wiki with no cited report of use); its range 3 to 25 mg per injection does not include the 28 mg of R2 or the 40 mg of R1

FOXO4-DRI

FOXO4-DRI at a glance

What is FOXO4-DRI?

FOXO4-DRI structure and chemistry