FOXO4-DRI Research Dosing: Published Animal and Cell Protocols

The human trial status review records our October 14, 2026 registry and PubMed searches. They did not identify a human treatment trial. This does not establish that the peptide has never been used outside a published or registered study.

The studies summarized here do not establish a safe human dose, validated human pharmacokinetics or a human therapeutic exposure. Converting a mouse dose by body size would not resolve those gaps.

These are selected protocols verified in primary methods; they are not an exhaustive inventory.

• Baar et al. 2017 (PMID 28340339): 5 mg/kg on three alternate days (days 1, 3 and 5). The doxorubicin arm used intravenous FOXO4-DRI; specified aging experiments used intraperitoneal administration. Renal outcomes were measured later, including at 30 days.
• Zhang et al. 2020 (PMID 31959736): 5 mg/kg intraperitoneally every other day for three administrations; assessments 30 days later.
• Han et al. 2022 (PMID 35510614): 5 mg/kg intraperitoneally on days 14, 16 and 18 after bleomycin, with analysis on day 21. Different schedules in the pirfenidone comparison arm cannot establish relative dosing efficiency in humans.
• Hu et al. (PMID 41625068): 5 mg/kg intraperitoneally every two days for a month in naturally aged mice and for four weeks in the D-galactose model. This is repeated dosing over weeks, unlike the original three-injection course.

Effects and tolerability must be interpreted within each model. These protocols do not establish an optimal dose, a general retreatment interval or safety in people.

Selected culture protocols used different concentrations and exposure periods:

• Baar 2017: 25 μM in selected assays (the paper also tested other concentrations) on senescent human IMR90 fibroblasts. The selectivity index (SI50) quantified how much more potently the peptide killed senescent versus control cells.
• Huang et al. 2021 (PMID 33996787): 25 μM for 5 days in 2% FBS medium on expanded healthy-donor human chondrocytes, followed by 2–3 days of recovery before analysis.
• Kong et al. 2025 (PMID 39994346): 25 μM for 3 days on serum-starved keloid fibroblasts, and a 3-day exposure at the same concentration in keloid organ cultures, followed through day 10.
• Hu et al. (online 2026) (PMID 41625068): 50 μM on endothelial (HUVEC) cultures under hypoxia and glucose deprivation.

Han 2022 measured full potency curves rather than picking a single concentration: the IC50 against TGF-β-activated mouse lung fibroblasts fell from 145 μM at 24 hours to 13 μM at 72 hours, and the peptide preferentially killed activated myofibroblasts over resting fibroblasts. This comparison involves a different activation model and does not establish the same selectivity across cell types.

The senolytic “hit-and-run” concept proposes that eliminating cells may produce effects after drug exposure ends. It does not show how long intact FOXO4-DRI remains in plasma or how quickly senescent cells reaccumulate in a particular tissue.

Both brief and longer regimens occur in the FOXO4-DRI literature. Human schedules for other senolytics cannot be transferred to this peptide.

A human development program would need a defined, reproducible product, appropriate formulation and route, exposure measurements, dose-related toxicology and controlled clinical evaluation. The original 46-residue D-peptide and later optimized compounds should not be treated as interchangeable.

These published experimental conditions are provided as research context. They do not establish a human administration protocol.