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Research profile · Peptide

FOXO4-DRI

Also known as FOXO4 D-retro-inverso peptide

Animal — evidence level 2 of 4: Animal evidenceExperimental — UK regulatory status: Experimental — not authorised for human use in the UK

Overview

A senolytic peptide designed to disrupt a protein interaction in senescent cells. One independent study found it worsened outcomes.

Category
Peptide
Highest evidence level identified
Animal evidence
Last scientifically reviewed
20 August 2026
Last regulatory review
20 August 2026

Mechanism under investigation

FOXO4-DRI is a retro-inverso peptide designed to disrupt the interaction between the transcription factor FOXO4 and the tumour suppressor p53. The proposal is that senescent cells depend on elevated FOXO4 to sequester p53 in the nucleus and so avoid programmed cell death, and that disrupting this causes selective apoptosis of senescent cells. A 2025 structural study reported that the peptide binds the relevant p53 domain to form a transiently folded complex, which offers support for target engagement.

Research areas

  • Cellular senescence
  • Ageing research

These are fields in which the compound has been investigated. Listing a field is not a statement that anything was demonstrated within it.

Current evidence

In-vitro evidence

Cells, tissues or biochemical systems outside a living organism.

Present, and includes genuinely independent work. Beyond the originating 2017 study, an independent group reported that the peptide removed more than half of senescent cells from heavily expanded primary human chondrocyte cultures while sparing minimally expanded controls — though it did not improve the cells’ regenerative capacity.

Animal evidence

Studies in living non-human animals.

The substantive tier, and genuinely mixed. The originating study reported restored fitness, fur density and renal function in fast-ageing and naturally aged mice. Independent groups have since reported activity in other models including ageing testicular tissue and pulmonary fibrosis. Critically, one independent study reported the opposite of benefit: in pulmonary arterial hypertension models, eliminating senescent cells by this route increased right ventricular pressure and hypertrophy and decreased pulmonary endothelial cells, leading the authors to caution that such intervention may worsen pulmonary haemodynamics.

Human observational evidence

Studies observing people without assigning an intervention.

None. No human administration of any kind was located.

Clinical-trial evidence

Studies assigning an intervention to human participants.

None. A registry search returned no studies involving this compound. It has never entered human trials.

Study limitations

  • The claims made for this compound in the context of ageing rest on a single 2017 paper. A title and abstract search returns only around seventeen records, roughly half of them reviews rather than primary research, and the headline findings in aged mice have not been independently repeated.
  • Independent primary work does exist, but it tests different endpoints in different disease models. It corroborates senolytic activity in general rather than replicating the original ageing results.
  • At least one independent study found that removing senescent cells by this route was harmful rather than beneficial, which indicates the effect is context-dependent and not uniformly favourable.
  • One supporting paper carries a published correction notice.
  • No human data of any kind exist — no pharmacokinetics, no dose-ranging, no safety study, no registered trial.

UK regulatory context

Experimental — not authorised for human use in the UK

A compound appearing in research literature that holds no UK authorisation for human use in any indication.

Source: The Human Medicines Regulations 2012, regulation 46 — prohibition on sale or supply of an unauthorised medicinal product (opens legislation.gov.uk in a new tab) (legislation.gov.uk)

Regulatory classification is jurisdiction-specific. A compound authorised elsewhere is not thereby authorised in the UK, and a supplier’s description of a substance does not determine how it is classified in law. See safety and regulation for the framework and the authoritative sources.

Safety and interpretation

There are no human safety data, as the compound has never been administered in a registered clinical trial. Animal work describes conditions under which it was reported to be well tolerated, but that supports no statement about humans. The 2023 finding that senolytic removal of pulmonary endothelial cells worsened haemodynamics in animal models illustrates that eliminating senescent cells is not inherently benign and may be harmful in some tissues.

References