FOXO4-DRI
also known as FOXO4-DRI, FOXO4 D-retro-inverso
D-retro-inverso peptide derived from the FOXO4 transcription factor's p53-binding domain. Disrupts FOXO4-p53 interaction selectively in senescent cells, triggering apoptosis while sparing healthy tissue. Cleared senescent cells in aged mice, restored cerebral blood flow, and improved physical function. Pre-clinical only — no human trials completed.
At a glance
SQ · Animal models only
Primary target — FOXO4-p53 protein complex in senescent cells [bourgeois-2025][tripathi-2021].
Pathway — FOXO4-DRI binds disordered p53 transactivation domain → displaces FOXO4 → nuclear p53 exclusion → p53-mediated apoptosis in senescent cells.
Downstream effect — Selective apoptosis of senescent cells; clearance restores tissue homeostasis [tripathi-2021][alameen-2026].
Origin — D-retro-inverso modification — inverted amino acid sequence, D-amino acids for protease resistance.
| Parameter | Value |
|---|---|
| Animal dose (mouse) | 5 mg/kgSQ injection, aged mouse model (testosterone restoration). |
| Frequency (animal) | Variable — single or intermittent dosingProtocol-dependent; no standardised regimen. |
| Human equivalent (theoretical) | ~0.4 mg/kg (28 mg / 70 kg adult)Extrapolated using allometric scaling; no clinical validation. |
| Evidence basis | Animal / mechanistic |
| Route | SQ (animal)No human route established. |
| Duration | Weeks to months (animal studies)Senescent cell clearance observed within weeks. |
| Clinical status | No human trials completed |
Reconstitution
A pure mass-to-volume utility. Enter what you have in the vial; the atlas computes the volume per dose. No prescription information.
- — Pulmonary hypertension or vascular disease (preclinical evidence of harm) [born-2023]
- — Pregnancy / lactation (no safety data)
- — Active malignancy (senescence as tumour suppressor mechanism)
- — Wound healing / tissue repair (senescent cells involved in fibrosis resolution)
- 01Pre-clinical route
Subcutaneous injection used in rodent models. No human administration protocol exists.
- 02Reconstitution (animal)
Typically reconstituted in sterile saline or PBS for animal experiments. Stability data limited.
- 03Dosing schedule
Variable — single bolus or intermittent dosing over weeks. No standardised human protocol.
- 04Clinical development status
No registered human trials. Commercialisation by Cleara Biotech (Netherlands) in development phase.
- 05Safety monitoring (proposed)
Would require cardiovascular assessment, pulmonary function, immune panel, tumour surveillance if human trials proceed.
Sources
of 45 rendered claims carry a resolvable citation.
- [alameen-2026]Alameen 2026 — Targeting the FOXO4-p53 axis by retro-inverso peptide senolytic agents: a pharmacological strategy to mitigate brain aging and cognitive decline.
journal, 2026 - [born-2023]Born 2023 — Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression.
journal, 2023 - [bourgeois-2025]Bourgeois 2025 — The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI.
journal, 2025 - [kohoutova-2025]Kohoutova 2025 — Structural plasticity of the FOXO-DBD:p53-TAD interaction.
journal, 2025 - [kong-2025]Kong 2025 — FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation.
journal, 2025 - [pawge-2021]Pawge 2021 — p53 regulated senescence mechanism and role of its modulators in age-related disorders.
journal, 2021 - [tripathi-2021]Tripathi 2021 — Development of a novel senolytic by precise disruption of FOXO4-p53 complex.
journal, 2021