FOXO4-DRI

DNot approved (preclinical)Mitochondrial, antioxidant and longevity compounds →FOXO4 D-retro-inverso peptidesenolytic peptideProxofim
In one paragraphFOXO4-DRI is a cell-penetrating peptide designed to pry the protein FOXO4 away from p53 inside senescent cells, causing those cells to die. In a 2017 Cell paper it restored fitness, fur density and kidney function in aged and prematurely ageing mice. That is the entire evidence base: no human trial, no human safety data, and no regulatory filing. Products sold under the name are unlicensed research chemicals.
Schematic 3D structure of FOXO4-DRI
46 residues · D-amino-acid retro-inverso peptide, unstructured · schematic
Overall gradeD No human evidence
Human trials0
Outcomes graded3
Last reviewed23 September 2026
EvidenceWhat it isHow it worksUnknownsMolecule & PKRegulationQuestionsReferences

What the human research shows

A genuinely interesting laboratory result that has not moved toward people in nine years. Grade D is a statement of what exists, not a verdict on the mechanism.

MetabolicCardioMuscleHealingNeuroImmuneSexualSkinAgeing

Evidence profile0–5

  • Metabolic & weight—0.0
  • Cardiovascular—0.0
  • Muscle & growth—0.0
  • Healing & repair—0.0
  • Neuro & sleep—0.0
  • Immune & inflammation—0.0
  • Sexual & hormonal—0.0
  • Skin & appearance—0.0
  • Ageing & longevity—0.0
No benefit outcome for FOXO4-DRI has both human evidence and a measurable effect, so the profile is empty. That is the finding, not a gap in the chart.
OutcomeGradeEffect sizeHuman studiesWhere the evidence comes from
Any outcome in humansDNo human evidenceNot measurable0No clinical study is registered or published. LYO's search found none.2
Fitness, fur density and renal function (aged mice)DNo human evidenceLargeAnimal onlyBaar and colleagues report selective clearance of senescent cells and functional restoration in fast-ageing and naturally aged mice, and protection against chemotherapy toxicity.1
Senescent cell clearance (human cells in vitro)DNo human evidenceModerateCell cultureRemoved senescent cells from expanded human chondrocytes in a 2021 study — the closest the compound has come to a human tissue.3
AMultiple good human trials, consistentBSome human trials, mostly consistentCFew or weak human studiesDAnimal or anecdotal onlyeffect size · red = adverse

Literature searched to 23 September 2026. Human studies only; animal and cell work informs the mechanism section and nothing else.

What it is

FOXO4-DRI is a 46-residue peptide built from D-amino acids in reverse order ('retro-inverso'), which makes it resistant to breakdown while keeping the shape of the FOXO4 region that binds p53. It was designed at the Erasmus Medical Center in Rotterdam by Peter de Keizer's group and published in Cell in 2017.

A start-up (Cleara Biotech) pursued a derivative, Proxofim, for cancer and ageing; no human trial has been announced. Meanwhile the original sequence is synthesised and sold online as a 'senolytic peptide'.

How it is thought to work

Senescent cells survive partly because FOXO4 holds p53 in the nucleus and away from the apoptosis programme. The peptide competes for that interaction, releases p53, and the senescent cell — but not its healthy neighbours — dies. The selectivity in mice was striking; whether it holds in people, and at what cost, is untested.

What is still unknown

  • Safety in humans: p53 is a tumour suppressor, and manipulating it is not trivial.
  • Dose, route and pharmacokinetics in any human — none reported.
  • Whether a 46-residue D-peptide is even what the vials contain; no product testing is public.

The molecule and how long it lasts

Identity
Formula
C228H388N86O64
Molecular weight
5358 g/mol
CAS number
2460055-10-9
PubChem
CID 167312269

Record is the TFA salt form

PubChem record, read 23 September 2026.

Pharmacokinetics
Route
Injected as sold; no human study
Half-life
No human pharmacokinetic data

No pharmacokinetic study in people.

Regulatory status

European Union
Not authorised

Preclinical; supply for human use is unlawful.

United States
Not approved

Not FDA-approved; no IND announced.

United Kingdom
Not licensed

Unlicensed.

Australia
Not on the ARTG

Not registered.

Canada
Not authorised

No Drug Identification Number.

Sport (WADA)
Prohibited at all times

Unapproved, so S0 (non-approved substances).

Questions people actually ask

Has FOXO4-DRI been tested in humans?
No. Not one trial, at any phase. The evidence is mice and cell culture.
Is FOXO4-DRI a senolytic?
In mice, yes — it selectively killed senescent cells. Whether it does so safely in people is unknown.
Why is it sold if untested?
Because the mouse paper was widely reported and the sequence is public. Availability online says nothing about safety or legality; it is an unapproved substance everywhere.

One page per claimed effect

References

  1. 1
  2. 2
  3. 3

Change log

  • 2026-09-23Initial publication. Grade D: no human study.