P Palthera
Synthetic Peptides

FOX04-DRI

FOXO4-DRI / FOXO4-D-Retro-Inverso / Proxofim

FOX04-DRI is a D-retro-inverso peptide designed by the Peter de Keizer group (Erasmus / Utrecht) to interfere with the FOXO4-p53 interaction in senescent cells. The intent is to selectively trigger apoptosis of senescent cells (a 'senolytic' approach). All published evidence is — rodent and work. There are no peer-reviewed clinical trials in humans.

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Synthetic Peptides
Classification
Synthetic D-retro-inverso senolytic peptide · Preclinical only
Research stage
Preclinical only — no human clinical trials indexed on PubMed
Sequence
LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRPPPPYLPPLLPPPPPP (D-retro-inverso configuration)
Molecular weight
Approximately 5230 Da (D-amino-acid construct)

Snapshot

Key takeaways

A three-bullet snapshot before reading the full dossier.

  1. 01

    Designed to disrupt the FOXO4-p53 protein–protein interaction in senescent cells.

  2. 02

    D-retro-inverso configuration is intended to improve protease resistance versus the L-peptide.

  3. 03

    All cited evidence is — rodent or models.

Dossier overview

3

research areas

2

references

3

handling notes

01

Mechanism of action

FOX04-DRI is reported to compete with FOXO4 for binding to p53 in senescent cells, releasing p53 to the nucleus and triggering apoptosis selectively in cells with a senescence-associated FOXO4-p53 retention pattern. Activity outside senescent populations has been less characterised.

02

Research applications

  • Senolytic mechanism studies
  • Tissue-ageing and fibrosis rodent models
  • Cell-culture senescence

Evidence at a glance

What's behind this profile

2 citations · 2020–2023

Animal
2

Studies in rodents or other animal models.

Publication years

  1. 20
  2. 21
  3. 22
  4. 23
20202023

Counts are derived from the cited studies below. A study covering both in vivo and in vitro work is counted by its primary model. Sample size is reported in 0 of 2 citations. Findings remain model-specific and are not extrapolated to therapeutic use.

03

Study references

Each profile cites a minimum of two peer-reviewed sources, with model type and reported sample size where the source provides it. Findings are model-specific and must not be extrapolated to therapeutic use.

FOXO4-D-Retro-Inverso senolytic peptide attenuates pulmonary hypertension in a model of bleomycin-induced pulmonary fibrosis

2023

Born E et al. · Circulation

Model
In vivo — bleomycin mouse model of pulmonary fibrosis / pulmonary hypertension
Sample
Not reported in abstract

Reported FOX04-DRI attenuated pulmonary hypertension and senescence markers in a bleomycin-induced rodent fibrosis model.

PMID 36515093 DOI 10.1161/CIRCULATIONAHA.122.061882

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

2020

Zhang C et al. · Aging

Model
In vivo — aged C57BL/6 mice plus in vitro Leydig-cell senescence assays
Sample
Not reported in abstract

Observed clearance of senescent Leydig cells and partial restoration of testosterone secretion in aged male mice treated with FOXO4-DRI.

PMID 31959736 DOI 10.18632/aging.102589

Evidence caveats

  • No controlled human trials indexed on PubMed at time of writing.
  • Findings are model-specific (rodent / in vitro) and are not extrapolated to therapeutic use.
  • Senolytic off-target effects on non-senescent cells require further independent characterisation.

04

Storage and handling

Typically stored in a cool, dry environment under controlled laboratory conditions per supplier documentation.

  • Use supplier documentation for batch-specific handling.
  • Limit repeated cycles during research inventory handling.
  • Document date and storage condition where applicable.

Common questions

FOX04-DRI FAQ

Plain-English answers backed by the citations on this profile — what it is, what's been studied, regulatory status, evidence limits.

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