FOXO4
FOXO4-DRI senolytic peptide reference entry; repository note added because market shorthand often says simply "FOXO4"
In peptide-market usage, "FOXO4" usually refers not to the endogenous FOXO4 transcription factor itself but to FOXO4-DRI, a synthetic senolytic peptide designed to disrupt the FOXO4-p53 interaction. Because that shorthand is ambiguous, the repository should make the distinction explicit. This entry is therefore built as a FOXO4-DRI research record, not as a normal endogenous-protein entry.
Key names include FOXO4-DRI, FOXO4 D-retro-inverso peptide, and informal shorthand such as FOXO4 peptide. The entry should also note that the endogenous target is the FOXO4 transcription factor, which is biologically distinct from the administered experimental peptide. No approved drug brand was identified.
3. Sequence and structure
FOXO4-DRI is a long synthetic all-D retro-inverso peptide derived from the FOXO4 interaction region and engineered for stability and cell entry. Public compound records place it in the multi-kilodalton range, around 5.36 kDa, and vendor or literature descriptions often include a highly basic cell-penetrating tail. Because naming and exact commercial constructs can vary, the repository should store the published research construct separately from any vendor-specific variant.
The peptide is designed to interfere with FOXO4-mediated sequestration of p53 in senescent cells. In preclinical models, that disruption can trigger selective apoptosis of some senescent cells and reduce senescence-associated tissue dysfunction. Mechanistically, this is one of the clearest senolytic peptide concepts in the literature, but it is still far from established clinical therapy.
Current use cases are investigational and include senescence biology, aging models, fibrosis and keloid research, cartilage-cell expansion models, and adjunctive cancer-senescence studies. None should be represented as approved anti-aging treatment indications. The repository should grade this entry as experimental and translational.
Human PK data were not identified. The D-retro-inverso design is meant to improve proteolytic stability relative to ordinary L-peptides, but route, tissue exposure, half-life, and immunogenicity remain insufficiently characterized in humans. ADME fields should therefore remain provisional.
The preclinical signal is notable. Mouse and cell-system studies report selective senescent-cell apoptosis and functional improvement in some aging or injury models, but no mature human efficacy package exists. Repository confidence should therefore be moderate for biologic plausibility and low for clinical translatability.
Human safety is essentially unestablished. The major concerns are off-target apoptosis, tissue-specific toxicity, immune reactivity, and the general uncertainty that comes with senolytic interventions affecting stress-response pathways. This is not a compound that should be described as "proven safe" outside controlled research.
No approved dosing standard exists. Any later dose information should be tied to named animal studies or protocol documents, not generalized into a consumer-use schedule.
UNVERIFIED RESEARCHER-REPORTED DOSING INFORMATION
The following dosing information has been compiled from community forums, researcher discussions, and gray-market sources. This information has NOT been verified through peer-reviewed scientific studies or clinical trials. It does NOT constitute medical advice, a prescription, or a recommendation for human use.
This data is presented solely for informational and educational purposes to document what is commonly discussed in research communities. Dosing protocols may be inaccurate, dangerous, or based on anecdotal reports with no scientific validation. Individual responses vary significantly, and unregulated compounds carry inherent risks including contamination, mislabeling, and unknown side effects.
Always consult qualified medical professionals before making any health-related decisions. The repository maintainers assume no liability for the use or misuse of this information.
Researcher-Reported Dosing Protocols
Common Dose Range: 250-500 mcg
Administration Route: Subcutaneous injection
Frequency: Once daily
Timing: Any consistent time of day
Schedule / Protocol: 8-16 week cycles
Dose Escalation: Start at 250 mcg daily for the first 4 weeks, increase to 375 mcg daily for weeks 5-8, and finally 500 mcg daily for weeks 9-16.
Additional Notes: Rotate injection sites to minimize local irritation.
This researcher-reported dosing information was compiled from unverified community sources and does not represent validated scientific or medical guidance.
No registered mainstream human clinical program was identified in this update. The evidence base remains preclinical and translational.
Not approved by the FDA or EMA. Best categorized as an investigational senolytic peptide.
13. References and source quality
Foundational sources include the 2017 Cell paper describing targeted apoptosis of senescent cells with FOXO4-DRI, later mechanistic and translational studies, and PubChem compound records for chemistry metadata. Source quality is good for preclinical mechanism and weak for human clinical use because that evidence is not yet established.
FOXO4-DRI is materially more complex to manufacture than short cosmetic peptides because it is a long D-peptide construct where stereochemistry, sequence fidelity, and purity are critical. Salt form and the presence or absence of a cell-penetrating segment should be captured explicitly in the repository schema.
Version 0.1 starter entry created March 14, 2026. Evidence basis for this draft: the foundational FOXO4-DRI Cell paper, later preclinical senolytic studies, and PubChem compound metadata.