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Longevity & bioregulatorsPeptideEvidence C3 cited

FOXO4-DRI

Senolytic Peptide

aka FOXO4-D-Retro-Inverso · proxofim

Experimental peptide researched for selectively triggering apoptosis in senescent, non-dividing cells.

Molecular wt
5358g/mol
Formula
C228H388N86O64
CAS
2460055-10-9
Route
Subcutaneous injection
PubChem
167312269

Sequence

Read this before quoting the sequence
A 46-residue D-retro-inverso (DRI) peptide: the FOXO4 p53-interacting segment is built from D-amino acids in reversed sequence order, fused to an L-amino-acid cell-penetrating (TAT-like, Arg/Lys-rich) carrier at the C-terminal end. A one-letter string would be misleading because it cannot express the D/L stereochemistry that defines the molecule. Sequence string as deposited on PubChem CID 168431240.
Source ↗

Mechanism of action

FOXO4-DRI is a peptide designed to interfere with the interaction between FOXO4 and p53 proteins. By disrupting this interaction, it selectively induces apoptosis in senescent cells, which are cells that have stopped dividing and contribute to aging and age-related diseases. This targeted action helps to clear these dysfunctional cells from tissues, potentially improving tissue function and health.

What the evidence actually shows

Grade C

There are currently no published human clinical trials for FOXO4-DRI. Most evidence comes from animal studies and in vitro experiments, which show promising senolytic effects. The lack of human data represents a significant gap in understanding its safety and efficacy in humans.

Regulatory status

Status
Not approved as a medicine in any jurisdiction identified. No entry in Drugs@FDA or the EMA medicines register.
Clinical stage
Preclinical only. All retrievable evidence is in vitro and mouse. No registered human trials identified.
WADA
Not named on the WADA 2026 Prohibited List. S0 (Non-Approved Substances) prohibits at all times 'any pharmacological substance ... with no current approval by any governmental regulatory health authority for human therapeutic use', which on its face covers FOXO4-DRI.
UK
research_compound

FOXO4-DRI is not approved for clinical use in the UK and is considered a research compound. It is not regulated by the MHRA for therapeutic use.

Source ↗

Dosing — what backs each figure

FOXO4-DRI is a senolytic retro-inverso peptide with no human data whatsoever - no registered trial, no published human dosing, no human safety data. The single well-characterised in vivo regimen is 5 mg/kg intraperitoneal on days 1, 3 and 5 in mice (Baar et al., Cell 2017), a route and species that give no basis for a human dose.

PreclinicalAnimal studies — not a human dose

  • 5 mg/kg intraperitoneally on days 1, 3 and 5 (3 doses, every other day); neutralised doxorubicin chemotoxicity and, in aged and Xpd(TTD/TTD) progeroid mice, restored fitness, fur density and renal function

    mouse (doxorubicin-treated, naturally aged 110+ weeks, and Xpd(TTD/TTD) fast-ageing) · intraperitoneal · PMID 28340339

Animal doses do not convert to human doses by body weight alone. Route matters too — a compound dosed intraperitoneally in mice tells you little about subcutaneous use.

Commonly circulatedNot established by any study
Dose
Variable — research protocols
Frequency
Pulsed protocols

Why this isn't evidence
'Variable - research protocols' and 'pulsed protocols' name no source and no number; the only real protocol in existence is 5 mg/kg intraperitoneally on days 1/3/5 in mice, and there is no ClinicalTrials.gov record or published human exposure of any kind.

This figure is shown because it is what circulates and what people search for — not because it is supported. Cycle lengths in particular tend to be convention copied between compounds rather than anything derived from a compound's own pharmacokinetics.

No established human dose
No approved label or completed human trial establishes a dosing regimen for this compound. Anything presented as a standard protocol for it — anywhere — is someone's convention rather than a finding.

Handling and storage

No compound-specific stability data exists
No compound-specific storage data exists in any regulatory label or published stability study that could be retrieved. FOXO4-DRI has no marketing authorisation. Only generic lyophilised-peptide handling guidance would apply. (D-amino-acid peptides are generally more protease-resistant than L-peptides, but no source giving specific temperatures or durations for this compound was found.) General peptide handling still applies — reconstitute gently, keep it cold, keep it dark — but any specific figure you see quoted for this compound elsewhere is someone's assumption, not a measurement.
→ Reconstitution walkthrough→ Reconstitution calculator

Safety

Commonly reported
  • ·Injection site reactions
  • ·Transient fatigue
Rarely reported
  • ·Potential for off-target effects leading to tissue damage
Contraindications
  • ·Pregnancy
  • ·Breastfeeding
  • ·"Active cancer"
Drug interactions
  • ·Chemotherapy agents, as FOXO4-DRI may alter their effects on senescent cells

Reported combinations

Reported as synergistic
  • ·Quercetin, which may enhance senolytic effects
Reported as antagonistic
  • ·Antioxidants, which may interfere with the apoptosis of senescent cells

Combination claims in this dataset are largely unsourced and should be treated as folk knowledge until a citation appears beside them.

References (3)

Data provenance

Chemistry and citations on this page were checked against primary sources on 2026-08-14. Values that could not be verified were left blank rather than filled with a plausible guess.

Could not verify
storage, reconstitution

Research use only
This profile is educational reference material. It is not medical advice, not a prescription, and not an endorsement of self-administration. Compounds discussed here are research chemicals and most are not approved for human therapeutic use.

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