Synthetic analog · 46 amino acids · 5,358.2 Da

FOXO4-DRI studies and research data

PepBank has 11 FOXO4-DRI studies with results. 10 of them gave FOXO4-DRI, with 39 results, grouped by what the studies measured. In each group, results from studies in people come first. Data as of 2026-10-30.

Searches 39 results and 19 papers. Newer studies from Europe PMC

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

The molecule

FOXO4-DRI identity

Identifiers, parent molecule, targets and development stage, from curated data.

FOXO4-DRI (FOXO4 D-Retro-Inverso) was described by Baar et al. in Cell in 2017 (PMID 28340339). The group of Peter de Keizer found that FOXO4 helps senescent cells to survive. They designed a peptide that disturbs the FOXO4 and p53 interaction. The peptide has two parts: a FOXO4 region that the authors chose because it is conserved in human and mouse but differs from FOXO1 and FOXO3, and an HIV-TAT cell-penetrating segment. All 42 chiral residues are D-amino acids (the 4 glycines have no D form) and the chain is written in reversed order, a retro-inverso design. The authors state that this design can give new chemical properties to a peptide. In NMR experiments the peptide competed with FOXO4 for binding to p53. In senescent human fibroblasts (IMR90) it caused p53 nuclear exclusion and apoptosis. In mice it was given as three injections of 5 mg/kg on alternate days. Under these conditions it was well tolerated. It reduced doxorubicin-induced toxicity and improved fitness, fur density and renal function in fast-ageing Xpd(TTD/TTD) mice and in naturally aged mice. Independent groups later used the peptide in senescent human chondrocytes (PMID 33996787), aged mouse Leydig cells (PMID 31959736), keloid fibroblasts (PMID 39994346), endothelial cells (PMID 41625068) and lung fibrosis models (PMID 35510614, PMID 37074394). A 2025 NMR study (PMID 40593617) found that the peptide binds the disordered p53 transactivation domain TAD2, that both the FOXO4-derived region and the cationic cell-permeability segment contribute to binding, and that p53 phosphorylation raises the affinity. The evidence is from cells and animals. Europe PMC, PubMed and ClinicalTrials.gov searches on 2026-10-13 found no registered human trial of FOXO4-DRI. The peptide is not approved by FDA or EMA. A Fight Aging! post of February 2026 says the company Cleara Biotech was formed to commercialise the work and "appears to still be a going preclinical concern", and that people can buy the peptide from sellers. The name Proxofim appears only on seller or secondary pages and no INN record was found.

Kind: Synthetic analog · 46 residues
Identifiers: PubChem CID167312269 (opens in a new tab)CAS2460055-10-9
Parent: Analog of Forkhead box protein O4 (FOXO4, human) · residues 91-124Retro-inverso peptide mimic of a FOXO4 region plus a fused HIV-TAT segment. Baar et al. 2017 say that FOXO4-DRI was designed from a FOXO4 region that is conserved in human and mouse and differs from FOXO1 and FOXO3. Reversing residues 1-34 of FOXO4-DRI and reading them as L-residues gives FOXO4 residues 91-124 of UniProt P98177 exactly (34 of 34 residues). The peptide has no FOXO4 sequence in the normal direction and carries 12 extra residues (P-P and the TAT segment), so it is not a fragment or a modified form of FOXO4. relation = analog_of. The source paper does not give residue numbers in the text; the numbering is our own match against UniProt. Q9UE68, given in the task brief, is a merged accession (now secondary to IL1R2, P27930); the human FOXO4 entry is P98177. FOXO4 has no seed record, so slug_ref is null and parent_positions is null; the range is given in uniprot_positions.
Development: PreclinicalAcademic 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).All published efficacy data are from cell culture and mice. ClinicalTrials.gov API v2 searches on 2026-10-13 for FOXO4-DRI, FOXO4 DRI, Proxofim, FOXO4 peptide, CL04177 and CL04183 returned 0 studies. A search for FOXO4 alone returned 1 unrelated study (a lymphoma trial). The Fight Aging! post of February 2026 says Cleara 'appears to still be a going preclinical concern focused more on the FOXO4-p53 interaction than on FOXO4-DRI per se' and that no useful data will come from personal use of seller peptide. The Cleara Biotech home page (clearabiotech.com, read 2026-10-13) names two lead development candidates, CL04177 and CL04183, aimed at cancer cells with impaired p53 signalling. It does not name FOXO4-DRI and it gives no date for a first-in-human study. A seller page (Remy Research) says a first-in-human study of CL04183 is planned for 2027. That date is NOT confirmed by any Cleara source and is not used as a fact here. The Cleara candidates are not the same substance as FOXO4-DRI. Source (opens in a new tab)

Targets

Molecular targets with action and evidence source
Target	Action	Evidence
Forkhead box protein O4 (FOXO4)FOXO4P98177 (opens in a new tab)	Disrupts the foxo4 p53 interaction (competes with foxo4 for p53)	primary literatureSource (opens in a new tab)
Cellular tumor antigen p53 (transactivation domain TAD2)TP53P04637 (opens in a new tab)	Binds p53 and displaces foxo4; causes p53 nuclear exclusion and apoptosis in senescent cells	primary literatureSource (opens in a new tab)

Sequence and structure

Residues, differences from the parent, calculated properties and 3D structure. Source values and calculated values are shown separately.

Sequence

46 amino acids · 2 modifications

H-

TLRKEPASE

IAQSILEAYS

QNGWANRRSG

GKRPPPRRRQ

RRKKRG

Parent: Forkhead box protein O4 (FOXO4, human)

No sequence is listed for the parent, so no alignment is shown.Retro-inverso peptide mimic of a FOXO4 region plus a fused HIV-TAT segment. Baar et al. 2017 say that FOXO4-DRI was designed from a FOXO4 region that is conserved in human and mouse and differs from FOXO1 and FOXO3. Reversing residues 1-34 of FOXO4-DRI and reading them as L-residues gives FOXO4 residues 91-124 of UniProt P98177 exactly (34 of 34 residues). The peptide has no FOXO4 sequence in the normal direction and carries 12 extra residues (P-P and the TAT segment), so it is not a fragment or a modified form of FOXO4. relation = analog_of. The source paper does not give residue numbers in the text; the numbering is our own match against UniProt. Q9UE68, given in the task brief, is a merged accession (now secondary to IL1R2, P27930); the human FOXO4 entry is P98177. FOXO4 has no seed record, so slug_ref is null and parent_positions is null; the range is given in uniprot_positions.

Properties

From identity sources

Formula: C₂₂₈H₃₈₈N₈₆O₆₄
Molecular weight: 5,358.2 g/mol
Monoisotopic mass: 5,354.975 Da

Curated PMC5556182 (Baar et al. 2017, STAR Methods)(opens in a new tab)retrieved 2026-10-13
PubChem CID 167312269(opens in a new tab)retrieved 2026-10-13
PubChem CID 167312269 and 168431240 (E-utilities esummary)(opens in a new tab)retrieved 2026-10-13
UniProt P98177(opens in a new tab)retrieved 2026-10-13
UniProt P04608(opens in a new tab)retrieved 2026-10-13
Curated Wikipedia FOXO4-DRI (CAS, PubChem CID, sequence)(opens in a new tab)retrieved 2026-10-13

Calculated from the sequence

pKa set

Some values cannot be calculated. A modification changes this value and is not modeled here (for example a lipid, metal or linker).

Average mass: Not calculated
Monoisotopic mass: Not calculated
Isoelectric point (pI): Not calculated
Net charge at pH 7.4: Not calculated
GRAVY (hydropathy): −1.633; Mean Kyte-Doolittle hydropathy · Kyte and Doolittle 1982; Negative: hydrophilic on average.
Extinction coefficient, 280 nm (Cys reduced): 6,990 M⁻¹ cm⁻¹; 5500 x Trp + 1490 x Tyr · Pace et al. 1995 (ExPASy ProtParam)
Instability index: 132.43; Dipeptide instability weights (DIWV) · Guruprasad et al. 1990; Above 40: classed as possibly unstable (ExPASy).
Aliphatic index: 51.1; Mole % A + 2.9 V + 3.9 (I + L) · Ikai 1980
Boman index: 4.35 kcal/mol; Mean solubility value (negated) · Boman 2003; Above 2.48: high protein-binding potential (Boman).
Hydrophobic moment (μH): 0.518; Eisenberg scale, 100° per residue, best 11-residue window · Eisenberg et al. 1982, 1984

Not included: other modification. Mass, charge and pI are not calculated; use the identity-source values.
D-amino acids have the same mass and charge as L forms. Hydrophobicity scales were measured on L forms.
Defined and validated for proteins; use with care for short peptides.
Assumes an ideal alpha helix. Many short peptides are not helical.

@pepdb/chem 0.2.0 · EMBOSS pKa set · ExPASy residue masses

Net charge by pH

No charge curve

A modification changes this value and is not modeled here (for example a lipid, metal or linker).

Composition

Hydrophobic20% (9)A I L
Aromatic4% (2)W Y
Positive30% (14)K R
Negative7% (3)E
Polar22% (10)N Q S T
Special17% (8)G P

46 residues. Each residue counts in one class; F and W count as aromatic.

A Ala4 · 9%

I Ile2 · 4%

L Leu3 · 7%

M Met0 · 0%

V Val0 · 0%

F Phe0 · 0%

W Trp1 · 2%

Y Tyr1 · 2%

H His0 · 0%

K Lys4 · 9%

R Arg10 · 22%

D Asp0 · 0%

E Glu3 · 7%

N Asn2 · 4%

Q Gln3 · 7%

S Ser4 · 9%

T Thr1 · 2%

C Cys0 · 0%

G Gly4 · 9%

P Pro4 · 9%

3D structure

PredictedAlphaFold DB · P98177

Loads the 3D viewer (3Dmol.js, about 150 KB) and the model file from AlphaFold DB (EMBL-EBI).

2D structure

FOXO4-DRI has 46 residues. A full-atom drawing is hard to read at this size; the sequence view is the reference.

SMILES fromPubChem CID 167312269(opens in a new tab)

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

Helical wheel

An ideal alpha-helix projection. It shows where the hydrophobic residues fall if the peptide folds as a helix. It does not show that it does.

μH, residues shown: 0.125
μH, best 11-residue window: 0.518
Arrow direction: 292°
Residues: 46 · 3 rings of 18

HydrophilicHydrophobic

Eisenberg consensus (normalized) scale · + K, R · − D, E

Assumes an ideal α-helix: 100° per residue, 3.6 residues per turn. The arrow is the mean hydrophobic moment (Eisenberg et al. 1984) and points at the hydrophobic face.

Show as table

Position	Residue	Angle	Eisenberg consensus (normalized)
1	L	0°	1.06
2	T	100°	-0.05
3	L	200°	1.06
4	R	300°	-2.53
5	K	40°	-1.50
6	E	140°	-0.74
7	P	240°	0.12
8	A	340°	0.62
9	S	80°	-0.18
10	E	180°	-0.74
11	I	280°	1.38
12	A	20°	0.62
13	Q	120°	-0.85
14	S	220°	-0.18
15	I	320°	1.38
16	L	60°	1.06
17	E	160°	-0.74
18	A	260°	0.62
19	Y	0°	0.26
20	S	100°	-0.18
21	Q	200°	-0.85
22	N	300°	-0.78
23	G	40°	0.48
24	W	140°	0.81
25	A	240°	0.62
26	N	340°	-0.78
27	R	80°	-2.53
28	R	180°	-2.53
29	S	280°	-0.18
30	G	20°	0.48
31	G	120°	0.48
32	K	220°	-1.50
33	R	320°	-2.53
34	P	60°	0.12
35	P	160°	0.12
36	P	260°	0.12
37	R	0°	-2.53
38	R	100°	-2.53
39	R	200°	-2.53
40	Q	300°	-0.85
41	R	40°	-2.53
42	R	140°	-2.53
43	K	240°	-1.50
44	K	340°	-1.50
45	R	80°	-2.53
46	G	180°	0.48

Results by area

FOXO4-DRI results by year and outcome

Counts are exact and come from studies that gave the peptide.

Studies by year

11 of 19 studies have results (58%), published 2020 to 2026. Top row: every study. Bottom row: studies with results about FOXO4-DRI, by class. The rows use different scales.

Studies
Human
Animal
Lab
Computer model
Natural levels, tool or combination only

Studies19 in all, 2017 to 2026

Studies with results11 in all, 2020 to 2026

Retracted studies are left out. A study with results in two classes counts in both.

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

What the studies measured

People first in each area, then animals, then lab cells. Counts are exact and come from studies that gave the peptide.

FOXO4-DRI studies on cells, genes and aging

17 results · people 0 · animals 5 · lab 12

Top 5 of 17 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
In mice prone to lung blood pressure problems, FOXO4‑DRI was linked to loss of lung blood vessel lining cells compared with controls.Circulation, 2023
In lab tests, aged cartilage cells showed less senescence with FOXO4‑DRI than without it.Frontiers in bioengineering and biotechnology, 2021

FOXO4-DRI studies on lungs and breathing

5 results · people 0 · animals 4 · lab 1

Top 3 of 5 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

FOXO4-DRI studies on sex hormones and fertility

4 results · people 0 · animals 3 · lab 1

4 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
In cells, FOXO4‑DRI improved the growth of sperm precursor cells in coculture with Leydig cells.Experimental gerontology, 2024

FOXO4-DRI studies on heart and blood vessels

3 results · people 0 · animals 2 · lab 1

3 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

FOXO4-DRI studies on cancer

2 results · people 0 · animals 1 · lab 1

2 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

FOXO4-DRI studies on receptors and cell signals

7 results · people 0 · animals 0 · lab 7

Top 5 of 7 results

In cells, FOXO4‑DRI stopped FOXO4 from binding to P53.Frontiers in bioengineering and biotechnology, 2025
In lab tests, FOXO4‑DRI bound phosphorylated p53 more strongly.Nature communications, 2025
In cells, FOXO4‑DRI moved p53 out of the nucleus in aged Leydig cells.Aging, 2020
In this study, FOXO4‑DRI changed where p53 sits inside the cell nucleus.Naunyn-Schmiedeberg's archives of pharmacology, 2023
In lab tests on keloid tissue cultures and cells, p53-pS15 left the cell nucleus after FOXO4‑DRI treatment.Communications biology, 2025

FOXO4-DRI studies on bones and joints

1 result · people 0 · animals 0 · lab 1

1 result

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

Trials and papers

FOXO4-DRI trials

Registered trials that test the peptide, with phase, status and dates. A dot marks trials with posted results.

StatusPhase

0 trials match. Highest phase first. Data from ClinicalTrials.gov.

No trial matches these filters.

Papers

Studies on this peptide. Some have results. The others have none yet.

Sort

Design

19 studies match. Retracted studies are left out.

Showing 18 of 19 studiesquery qry_eaba82e218440988a80d06c3

Studies with results

11 studies

Animal study (in vivo) · mouse · 2023

2 results

Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression.

Born et al. 2023Circulationcited by 136

PMID 36515093DOI 10.1161/circulationaha.122.058794PUB-36515093

Full text at the publisher2 results where FOXO4-DRI was given

Publisher page See results (2)

Animal study (in vivo) · 2021

4 results

Targeting senescence-like fibroblasts radiosensitizes non-small cell lung cancer and reduces radiation-induced pulmonary fibrosis.

Meng et al. 2021JCI insightcited by 112

PMID 34877934PMC8675198DOI 10.1172/jci.insight.146334PUB-34877934

CC BY4 results where FOXO4-DRI was given

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Animal study (in vivo) · mouse · 2020

4 results

FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice.

Zhang et al. 2020Agingcited by 85

PMID 31959736PMC7053614DOI 10.18632/aging.102682PUB-31959736

CC BY4 results where FOXO4-DRI was given

Download PDF See results (4)

In vitro (cells) · 2021

5 results

Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes.

Huang et al. 2021Frontiers in bioengineering and biotechnologycited by 42

PMID 33996787PMC8116695DOI 10.3389/fbioe.2021.677576PUB-33996787

CC BY5 results where FOXO4-DRI was given

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Animal study (in vivo) · rat · 2024

3 results

Cellular Senescence Contributes to the Progression of Hyperoxic Bronchopulmonary Dysplasia.

Jing et al. 2024American journal of respiratory cell and molecular biologycited by 32

PMID 37874230PMC12042139DOI 10.1165/rcmb.2023-0038ocPUB-37874230

Rights unknown3 results where FOXO4-DRI was given

Source link See results (3)

In vitro (cell-free) · 2025

3 results

The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI.

Bourgeois et al. 2025Nature communicationscited by 17

PMID 40593617PMC12216184DOI 10.1038/s41467-025-60844-9PUB-40593617

CC BY1 result where FOXO4-DRI was given (plus 2 on tools or combinations, listed separately)

Download PDF See results (3)

Ex vivo tissue · 2025

3 results

FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation.

Kong et al. 2025Communications biologycited by 16

PMID 39994346PMC11850796DOI 10.1038/s42003-025-07738-0PUB-39994346

Free to read · publisher termsCC BY-NC-ND3 results where FOXO4-DRI was given

Read at source See results (3)

Animal study (in vivo) · mouse · 2024

5 results

FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells.

Li et al. 2024Experimental gerontologycited by 11

PMID 39025385DOI 10.1016/j.exger.2024.112522PUB-39025385

Full text at the publisher5 results where FOXO4-DRI was given

Publisher page See results (5)

Animal study (in vivo) · mouse · 2023

4 results

FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice.

Liu et al. 2023Naunyn-Schmiedeberg's archives of pharmacologycited by 8

PMID 37074394DOI 10.1007/s00210-023-02452-2PUB-37074394

Full text at the publisher4 results where FOXO4-DRI was given

Publisher page See results (4)

Animal study (in vivo) · mouse · 2025

8 results

FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway.

Hu et al. 2025Frontiers in bioengineering and biotechnologycited by 1

PMID 41625068PMC12852416DOI 10.3389/fbioe.2025.1729166PUB-41625068

CC BY8 results where FOXO4-DRI was given

Download PDF See results (8)

Not a test of FOXO4-DRI alone · 2026

2 results

Acylglycerol Kinase Sensitizes Glioblastoma to Temozolomide via Limiting Mitochondrial Damage Related Cellular Senescence.

Ning et al. 2026Molecular carcinogenesiscited by 1

PMID 42391447PMC13466165DOI 10.1002/mc.70134PUB-42391447

Rights unknown2 results where FOXO4-DRI was a tool, carrier or part of a combination

Source link See results (2)

More studies

7 studies

PubMed tag: article-commentary · 2017

Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.

Baar et al. 2017Cellcited by 1,181

PMID 28340339PMC5556182DOI 10.1016/j.cell.2017.02.031PUB-28340339

Rights unknown

Source link

PubMed tag: review-article, Review · 2018

Cellular senescence in the aging and diseased kidney.

Valentijn et al. 2018Journal of cell communication and signalingcited by 140

PMID 29260442PMC5842195DOI 10.1007/s12079-017-0434-2PUB-29260442

CC BY

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Indexing hint: Animal study · 2022

Corrected

FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway.

Han et al. 2022Journal of cellular and molecular medicinecited by 36

PMID 35510614PMC9170815DOI 10.1111/jcmm.17333PUB-35510614

CC BY

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PubMed tag: Review · 2017

[Molecular regulative mechanisms of aging and interventional effects of Chinese herbal medicine].

Liu et al. 2017Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medicacited by 2

PMID 29171222DOI 10.19540/j.cnki.cjcmm.20170731.001PUB-29171222

Full text at the publisher

Publisher page

PubMed tag: none · 2024

Correction to "FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway"Han XD, Yuan T, Zhang JL, 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.

Journal of cellular and molecular medicine

PMID 39166551PMC11337111DOI 10.1111/jcmm.18502PUB-39166551

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PubMed tag: Review · 2026

Targeting the FOXO4-p53 axis by retro-inverso peptide senolytic agents: a pharmacological strategy to mitigate brain aging and cognitive decline.

Alameen et al. 2026Naunyn-Schmiedeberg's archives of pharmacology

PMID 42024235DOI 10.1007/s00210-026-05309-6PUB-42024235

Full text at the publisher

Publisher page

PubMed tag: review-article, Review · 2026

FOXO4 as a Redox-Sensitive Regulator of Antioxidant Defense and Cellular Senescence: Cysteine-Based Signaling, p53 Interaction, and Therapeutic Targeting.

Mateescu et al. 2026Antioxidants (Basel, Switzerland)

PMID 42510573PMC13404206DOI 10.3390/antiox15070842PUB-42510573

CC BY

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No result for FOXO4-DRI (1 study on this page)

These studies name FOXO4-DRI but give no result for it (for example, the results concern another peptide in the study).

PubMed tag: none · 2017

Rejuvenation by Therapeutic Elimination of Senescent Cells.

Krimpenfort et al. 2017Cellcited by 21

PMID 28340347DOI 10.1016/j.cell.2017.03.014PUB-28340347

Rights unknown

Source link

Newer studies

PepBank reads each paper before it shows the results. This search looks in Europe PMC for newer papers that PepBank has not read yet.

FOXO4-DRI studies: 11 papers with results

Page 1 of 1

Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression.
Born E · Circulation · 2023
Animal study (in vivo) · mouse · 2 results
Targeting senescence-like fibroblasts radiosensitizes non-small cell lung cancer and reduces radiation-induced pulmonary fibrosis.
Meng J · JCI insight · 2021
Animal study (in vivo) · 4 results
FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice.
Zhang C · Aging · 2020
Animal study (in vivo) · mouse · 4 results
Cellular Senescence Contributes to the Progression of Hyperoxic Bronchopulmonary Dysplasia.
Jing X · American journal of respiratory cell and molecular biology · 2024
Animal study (in vivo) · rat · 3 results
FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells.
Li Y · Experimental gerontology · 2024
Animal study (in vivo) · mouse · 5 results
FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice.
Liu Y · Naunyn-Schmiedeberg's archives of pharmacology · 2023
Animal study (in vivo) · mouse · 4 results
FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway.
Hu Z · Frontiers in bioengineering and biotechnology · 2025
Animal study (in vivo) · mouse · 8 results
FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation.
Kong YX · Communications biology · 2025
Ex vivo tissue · 3 results
Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes.
Huang Y · Frontiers in bioengineering and biotechnology · 2021
In vitro (cells) · 5 results
The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI.
Bourgeois B · Nature communications · 2025
In vitro (cell-free) · 3 results
Acylglycerol Kinase Sensitizes Glioblastoma to Temozolomide via Limiting Mitochondrial Damage Related Cellular Senescence.
Ning N · Molecular carcinogenesis · 2026
Not a test of FOXO4-DRI alone · 2 results

Status and safety

Regulatory and safety

Approval and sport status, and the safety outcomes reported in study results. Laws and labels change, so check the regulator for the current status.

Regulatory status by jurisdiction, with date and source
Jurisdiction	Body	Status	As of	Source
US	FDA	No Drugs@FDA record: openFDA drugsfda searches for active ingredient FOXO4 and PROXOFIM returned no matches on 2026-10-13. FDA orphan designation and FDA warning-letter databases were not checked.	13 Oct 2026	fda.gov (opens in a new tab)
EU	EMA	No match for FOXO4, Proxofim, retro-inverso or forkhead in the EMA medicines data file (2,748 records, timestamp 2026-10-13T06:02:34Z). The orphan designations file (3,310 records, timestamp 2026-10-13T06:05:30Z) has one unrelated match: a cell product that carries a forkhead box protein N1 gene (EU/3/24/2924), which is a different protein.	13 Oct 2026	ema.europa.eu (opens in a new tab)
Sport	WADA	Banned in sport (WADA S0) S0 covers substances not approved for human use; FOXO4-DRI is not named on the List.	2026 List	wada-ama.org (opens in a new tab)
World (WADA 2027 list)	Note	S0 text of the 2027 Prohibited List (in force from 2027-01-01) is the same as in 2026 except that the examples now include 'peptides'. FOXO4-DRI is not named.	13 Oct 2026	wada-ama.org (opens in a new tab)
Russia (State Register of Medicines)	Note	not checked	13 Oct 2026	Not recorded
Japan (PMDA)	Note	not checked	13 Oct 2026	Not recorded

Safety outcomes

Reported effects from study results.

No safety results from studies in people

The studies with results report no safety outcomes for this peptide. That does not mean it is safe.

Doses studied

The doses that these studies used. They are not recommendations.

No dose was reported in the study results.

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

Data

Data and API

Data version, change history and code for this peptide.

Data version 30856030 Oct 2026

Peptide

Peptide id: PEP-000051
Peptide version: 6
Peptide hash: 8c550045ec7e2800…
Data version: 308560

Latest changes

27 Oct 2026UpdatedData version 256682
22 Oct 2026UpdatedData version 254517
21 Oct 2026UpdatedData version 213613
14 Oct 2026UpdatedData version 194687
13 Oct 2026UpdatedData version 188872
13 Oct 2026CreatedData version 175769

For developers

curl -s https://pepbank.io/v1/briefs/foxo4-dri

Evidence summary for FOXO4-DRI: counts by class, key results with sources, notices, data version.

Peptide as JSON Evidence summary as JSON

Outcome group	Human	Animal	Lab	Computer model	Total
Cell viability and deathSkin and wound	No results	Animal: 1 result from 1 study: 1 decrease. Strongest design: Animal study (in vivo)	Lab: 8 results from 6 studies: 5 increase, 2 decrease, 1 no significant change. Strongest design: Ex vivo tissue	No results	9
Aging markersRespiratory	No results	Animal: 4 results from 3 studies: 2 increase, 2 decrease. Strongest design: Animal study (in vivo)	Lab: 4 results from 3 studies: 4 decrease. Strongest design: In vitro (cells)	No results	8
Receptor activity and mechanismSkin and wound	No results	No results	Lab: 7 results from 5 studies: 4 increase, 2 decrease, 1 not reported. Strongest design: Ex vivo tissue	No results	7
Lung injury and fibrosisRespiratory	No results	Animal: 4 results from 3 studies: 1 increase, 3 decrease. Strongest design: Animal study (in vivo)	Lab: 1 result from 1 study: 1 decrease. Strongest design: In vitro (cells)	No results	5
Sex hormones and fertilityReproductive and sexual health	No results	Animal: 3 results from 2 studies: 3 increase. Strongest design: Animal study (in vivo)	Lab: 1 result from 1 study: 1 increase. Strongest design: In vitro (cells)	No results	4
Tumor growthCancer	No results	Animal: 1 result from 1 study: 1 increase. Strongest design: Animal study (in vivo)	Lab: 1 result from 1 study: 1 increase. Strongest design: In vitro (cells)	No results	2
Vascular functionCardiovascular	No results	Animal: 1 result from 1 study: 1 increase. Strongest design: Animal study (in vivo)	Lab: 1 result from 1 study: 1 increase. Strongest design: In vitro (cells)	No results	2
Bone and jointMusculoskeletal	No results	No results	Lab: 1 result from 1 study: 1 no significant change. Strongest design: In vitro (cells)	No results	1
Cardiovascular eventsRespiratory	No results	Animal: 1 result from 1 study: 1 not reported. Strongest design: Animal study (in vivo)	No results	No results	1

Outcome group	Human	Animal	Lab	Computer model	Total
Cell viability and deathSkin and wound	No results	Animal: 1 result from 1 study: 1 decrease. Strongest design: Animal study (in vivo)	Lab: 8 results from 6 studies: 5 increase, 2 decrease, 1 no significant change. Strongest design: Ex vivo tissue	No results	9
Aging markersRespiratory	No results	Animal: 4 results from 3 studies: 2 increase, 2 decrease. Strongest design: Animal study (in vivo)	Lab: 4 results from 3 studies: 4 decrease. Strongest design: In vitro (cells)	No results	8
Receptor activity and mechanismSkin and wound	No results	No results	Lab: 7 results from 5 studies: 4 increase, 2 decrease, 1 not reported. Strongest design: Ex vivo tissue	No results	7
Lung injury and fibrosisRespiratory	No results	Animal: 4 results from 3 studies: 1 increase, 3 decrease. Strongest design: Animal study (in vivo)	Lab: 1 result from 1 study: 1 decrease. Strongest design: In vitro (cells)	No results	5
Sex hormones and fertilityReproductive and sexual health	No results	Animal: 3 results from 2 studies: 3 increase. Strongest design: Animal study (in vivo)	Lab: 1 result from 1 study: 1 increase. Strongest design: In vitro (cells)	No results	4
Tumor growthCancer	No results	Animal: 1 result from 1 study: 1 increase. Strongest design: Animal study (in vivo)	Lab: 1 result from 1 study: 1 increase. Strongest design: In vitro (cells)	No results	2
Vascular functionCardiovascular	No results	Animal: 1 result from 1 study: 1 increase. Strongest design: Animal study (in vivo)	Lab: 1 result from 1 study: 1 increase. Strongest design: In vitro (cells)	No results	2
Bone and jointMusculoskeletal	No results	No results	Lab: 1 result from 1 study: 1 no significant change. Strongest design: In vitro (cells)	No results	1
Cardiovascular eventsRespiratory	No results	Animal: 1 result from 1 study: 1 not reported. Strongest design: Animal study (in vivo)	No results	No results	1

FOXO4-DRI studies and research data

FOXO4-DRI identity

Targets

Sequence and structure

Sequence

Parent: Forkhead box protein O4 (FOXO4, human)

Properties

Net charge by pH

Composition

3D structure

2D structure

Helical wheel

FOXO4-DRI results by year and outcome

What the studies measured

FOXO4-DRI studies on cells, genes and aging

FOXO4-DRI studies on lungs and breathing

FOXO4-DRI studies on sex hormones and fertility

FOXO4-DRI studies on heart and blood vessels

FOXO4-DRI studies on cancer

FOXO4-DRI studies on receptors and cell signals

FOXO4-DRI studies on bones and joints

FOXO4-DRI trials

Papers

Studies with results

Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression.

Targeting senescence-like fibroblasts radiosensitizes non-small cell lung cancer and reduces radiation-induced pulmonary fibrosis.

FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice.

Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes.

Cellular Senescence Contributes to the Progression of Hyperoxic Bronchopulmonary Dysplasia.

The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI.

FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation.

FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells.

FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice.

FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway.

Acylglycerol Kinase Sensitizes Glioblastoma to Temozolomide via Limiting Mitochondrial Damage Related Cellular Senescence.

More studies

Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.

Cellular senescence in the aging and diseased kidney.

FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway.

[Molecular regulative mechanisms of aging and interventional effects of Chinese herbal medicine].

Targeting the FOXO4-p53 axis by retro-inverso peptide senolytic agents: a pharmacological strategy to mitigate brain aging and cognitive decline.

FOXO4 as a Redox-Sensitive Regulator of Antioxidant Defense and Cellular Senescence: Cysteine-Based Signaling, p53 Interaction, and Therapeutic Targeting.

Rejuvenation by Therapeutic Elimination of Senescent Cells.

Newer studies

FOXO4-DRI studies: 11 papers with results

Regulatory and safety

Doses studied

Data and API

Peptide

Latest changes

For developers

Related peptides

FOXO4-DRI results by year and outcome

FOXO4-DRI studies on cells, genes and aging

FOXO4-DRI studies on lungs and breathing

FOXO4-DRI studies on sex hormones and fertility

FOXO4-DRI studies on heart and blood vessels

FOXO4-DRI studies on cancer

FOXO4-DRI studies on receptors and cell signals

FOXO4-DRI studies on bones and joints

FOXO4-DRI trials

Papers

Studies with results

Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression.

Targeting senescence-like fibroblasts radiosensitizes non-small cell lung cancer and reduces radiation-induced pulmonary fibrosis.

FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice.

Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes.

Cellular Senescence Contributes to the Progression of Hyperoxic Bronchopulmonary Dysplasia.

The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI.

FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation.

FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells.

FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice.

FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway.

Acylglycerol Kinase Sensitizes Glioblastoma to Temozolomide via Limiting Mitochondrial Damage Related Cellular Senescence.

More studies

Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.

Cellular senescence in the aging and diseased kidney.

FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway.

[Molecular regulative mechanisms of aging and interventional effects of Chinese herbal medicine].

Targeting the FOXO4-p53 axis by retro-inverso peptide senolytic agents: a pharmacological strategy to mitigate brain aging and cognitive decline.