FOXO4-DRI

Areas of active research — not promised effects

Each tag links to other compounds with research into that goal. Research use only: these are areas of study, not human-use claims.

Related by research scope · open each to compare

FOXO4-DRI has no FDA-approved indication and is not authorized for human clinical use outside of a registered IND. It does not appear on the FDA Category 2 bulk drug substances list that was subject to the April 2026 reclassification process (docket FDA-2025-N-6895). It therefore has no compounding pathway in the US. Sale for human use or as a dietary supplement is prohibited under the FD&C Act. Legitimate use is restricted to licensed research institutions and qualified researchers.

Transparent blend · bci-1.0 · never paid-placement

Primary name

FOXO4-DRI

Origin

FOXO4-DRI (also designated Proxofim) is a 40-residue D-retro-inverso (DRI) peptide derived from a fragment of the FOXO4 forkhead transcription factor. It was engineered by inverting the amino acid sequence and substituting all L-amino acids with their D-enantiomers, producing a protease-resistant mimic of the native FOXO4 segment that retains the capacity to bind p53. The design was reported by Baar and colleagues at Erasmus University Medical Center in a foundational 2017 Cell publication. CAS: 2460055-10-9; PubChem CID: 167312269; molecular formula C228H388N86O64; MW ~5358 Da.

Registry IDs

PubChem CID

167312269

CAS

2460055-10-9

InChIKey

WVZCDZFJLXBWHG-XXZPGMBKSA-N

Molecular formula

C228H388N86O64

Molar mass

5358 g/mol

Monoisotopic

5354.9750124 Da

InChIKey

WVZCDZFJLXBWHG-XXZPGMBKSA-N

Appearance

White to off-white lyophilized powder (vendor-typical)

Solubility

Soluble in water and dilute aqueous buffers; peptide contains multiple charged r…

Sequence not available in current seed.

Stability: D-retro-inverso configuration provides substantially greater protease resistance than equivalent L-amino acid peptides. Stability in aqueous solution is pH-sens

Vial sizes

5 mg · 10 mg

Purity grades

≥95% (HPLC) / ≥98% (HPLC)

Salt forms

Free base (primary)

• GHS hazard class on file
• PPE & spill response
• Disposal guidance
• Not-for-human-consumption posture

How much research exists, and of what maturity — never a verdict on whether it works.

Mechanism of action

• In senescent cells, FOXO4 forms a nuclear complex with p53 that suppresses pro-apoptotic p53 transcriptional activity and thereby maintains senescent cell viability
• FOXO4-DRI competitively binds to p53 at its TAD2 transactivation domain, displacing endogenous FOXO4 and causing p53 to translocate from the nucleus to the cytoplasm
• This cytoplasmic p53 then activates a transcription-independent apoptotic program—evidenced by increased BAX expression, caspase-3 cleavage, and decreased BCL-2—selectively in cells where the FOXO4–p53 interaction is elevated 10–20-fold relative to proliferating counterparts
• Proliferating and post-mitotic cells are largely spared, as their lower basal FOXO4–p53 occupancy provides little binding substrate for the DRI peptide at therapeutic concentrations studied preclinically

Pharmacokinetics (ADME)

Half-life

Not formally characterized in published pharmacokinetic studies; D-retro-inverso configuration is expected to extend half-life substantially (estimated hours vs. minutes for L-peptide counterpart) based on protease-resistance rationale

Clearance

Route and rate of clearance not reported in peer-reviewed literature; no published human PK data

PK–PD note: All PK inferences derive from the structural rationale of D-amino acid peptidase resistance; no validated PK/PD model in any species is published. Murine in vivo studies (5 mg/kg IV, every 3 days × 3 …

Reading the evidence

• Evidence quality and gaps vary by application — see the cited grades above.
• Indexed-article counts span all evidence tiers, not only completed human trials.
• No first-party human-dosing, efficacy, or benefit claims are made here.

Key reviews & evidence-gap sources

• Tripathi U et al. Development of a novel senolytic by precise disruption of FOXO4-p53 complex. eBioMedicine. 2021;74:103693 (commentary/review) — Anchoring review situating FOXO4-DRI (Baar 2017) within FOXO4-p53 senolytic peptide class; notes ES2 peptides 3-7x more potent than FOXO4-DRI in vitro/in vivo
• Baar MP et al. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell. 2017;169(1):132-147.e16 — Original/primary publication describing FOXO4-DRI design and senolytic mechanism; mouse + in vitro, no human trials
• The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI. Nature Communications. 2025 — Mechanistic structural study of FOXO4-DRI target (p53 transactivation domain)

No registered human trials found for this compound.

Status

No registered trials found

Summary (literature)

Formal toxicology studies in humans have not been published; FOXO4-DRI has not entered any registered clinical trial as of May 2026. In the 2017 Baar et al. mouse study, treated animals showed no overt signs of systemic toxicity, and blood panels remained within normal ranges. Se…

WADA status

Not specifically named in the WADA 2026 Prohibited List; however, FOXO4-DRI would fall under WADA S0 (Non-Approved Substances) as a pharmacological agent not ap…

Dominant research route: Intravenous (IV) — tail-vein injection at 5 mg/kg, three times per week, in aged and chemotherapy-treated mice (Baar et al., 2017, Cell); this is the sole published reference protocol for dose, route, and frequency.

5 mg/kg, three times per week for several weeks, in naturally aged mice (>24 months) and doxorubicin-treated (chemotherapy-induced senescence) mice; tail-vein injection (Baar et al., 2017, Cell)

Bioavailability: Systemic distribution achieved via tail-vein IV in mice; no human PK data exist. The Baar 2017 study is the sole published reference for dose, route, and frequency of FOXO4-DRI.

Dominant preclinical research route. Outcomes included restored fur density, improved exploratory behavior, and improved renal function (serum creatinine, urea nitrogen) versus controls. No human trials have used this route.

5 mg/kg intraperitoneal injection every other day for three administrations in aged mice (Leydig-cell / testosterone study); IP injection in D-galactose-induced progeroid and naturally aged mouse aortic/endothelial study

Bioavailability: IP route used in subsequent (post-Baar) mouse studies; no comparative PK vs IV published. Some secondary aggregator sources misattribute the original Baar 2017 study to IP rather than IV.

Used in follow-on rodent senescence models (testicular Leydig cells, vascular endothelium). Not evaluated against IV for bioavailability or senolytic efficacy.

Treatment of in-vitro-expanded human chondrocytes (PDL9) and senescent endothelial cells (OGD-induced); selective apoptosis of senescent cells with sparing of low-PDL/non-senescent cells

Bioavailability: Not a systemic route; no absorption/PK applicable. Demonstrates cell-level selectivity of FOXO4-DRI for senescent vs non-senescent cells.

Huang et al. 2021 (Front Bioeng Biotechnol) showed FOXO4-DRI removed >50% of PDL9 senescent chondrocytes without significantly affecting PDL3 cells. Hu et al. 2026 showed p53/BCL-2/Caspase-3-mediated apoptosis in senescent endothelial cells.

No published animal or human PK/senolytic study uses SC; community/anecdotal protocols only (de-identified aggregate: fixed doses in the low-mg range, intermittent 'hit-and-run' cycles)

Bioavailability: No published bioavailability data for SC FOXO4-DRI. Community sources note unknown bioavailability differences versus the IV route used in mouse studies.

Dominant community-reported route, but unsupported by any cited PK or efficacy study. Route confusion between animal (IV/IP) and community (SC) use is a frequently noted confounder.

Not studied in any animal or human model; no oral bioavailability or stability data published

Bioavailability: Oral bioavailability expected to be negligible given the peptide's large size; SC or IV delivery would likely be required for any systemic application. This is a mechanistic inference, not measured oral absorption.

No oral dosing studies exist. Modified versions with improved pharmacokinetics (longer half-life, better tissue penetration, potentially oral bioavailability) are described as under development, not realized.

Animal & human figures are kept visibly separate so studied animal doses are never misread as human guidance.

Sorted A–Z by vendor — never by price

Weekly median $/mg from the live vendor crawl.

Researched storefront prices, bucketed

p25 $18.00 · median $23.91 · p75 $25.06 · 8 researched vendors

Legit, COA-backed band: $23.00–$28.00/mg.

Value rule: don't just buy the cheapest — a price under $3/mg is a red flag. Pair price with COA and independent-test grade.

Estimated cost of research (10 mg)

Vial (best researched price)

$160

Bacteriostatic water (generic estimate)

$6

Syringes / supplies (generic estimate)

$12

What each test proves — general guidance, plus this compound's researched purity data

Purity on the current market (researched)

Vendor-reported COA purities of 99.0%–99.8% (HPLC) are common across suppliers; e.g., Skye Peptides reports 99.8% (batch FOX26-15-001), VPeptide reports avg 99.724%, and multiple vendors cite '≥99%' with Janoshik-issued COAs. These are vendor-supplied lot documents, not independent aggregator test data.

Independent labs cited for this compound

No FDA recalls, market withdrawals, or safety alerts specific to FOXO4-DRI were found in FDA enforcement databases as of June 2026. None found.

Buyer red-flag checklist

• No FDA-approved drug application; no human clinical trials completed — all efficacy claims are preclinical (mouse/in vitro) only.
• Vendor-issued COAs (predominantly Janoshik) are the sole purity evidence; no independent community-aggregate lab testing datasets found for this compound.
• Fabricated vendor/blog claims (e.g., specific percent lifespan extension) not supported by the original 2017 source publication.
• An 'RUO' label does not exempt peptide imports from DWPE under Import Alert 66-41; FDA evaluates actual marketed/intended use.
• No compound-specific FDA warning letters, recalls, or seizures located — but class-level enforcement (unapproved new drug peptides) is active and ongoing.

GMP vs research-grade: the chemistry (SPPS + HPLC + MS) is identical — the difference is the quality system.

Underdosing / mislabeling: No independent third-party lab-test aggregates (Janoshik/MZ Biolabs/Finnrick community datasets) reporting underdosing prevalence for FOXO4-DRI were located. Available purity data is limited to vendor-issued COAs.

• Detention Without Physical Examination of Unapproved New Drugs Promoted In The U.S. Authorizes FDA field divisions to detain peptide imports at the border under the 'appears-to-violate' standard (FD&C Act §801) without opening or testing each parcel. Last revised 05/19/2026. Applies to unapproved new drugs without an approved §505 application — a category encompassing FOXO4-DRI. Class-level alert; FOXO4-DRI is not individually named on the Red List.66-41
• An RUO label is not an import exemption — CBP judges actual intended use.
• Lyophilized powder is ambient-stable in transit; temperature control needed for > 7-day transit.
• US-warehouse vendors dodge import scrutiny — they cost more but ship more reliably.

Every item dated & sourced

Not specifically named on the WADA Prohibited List. Falls under S0 (Non-approved Substances) catch-all: 'Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use.' S0 substances are prohibited at all times and are Specified Substances.

No granted patents identified in current seed. Composition-of-matter coverage is limited given the peptide's synthetic origin.

• IACUC / IRB research context
• RUO buyer responsibilities & documentation
• Veterinary / alternative-use where lawful
• Jurisdiction-aware "who may lawfully obtain"

What people discuss

Reported concerns — discussion, not established effects

Reading caveats

• Self-experimenter sample is small and self-selected
• No human clinical trials exist; all efficacy framing is preclinical extrapolation
• Several aggregator blogs are vendor-affiliated or carry affiliate procurement links
• High unit cost skews discourse toward affluent biohacker demographic
• Anecdotal reports cannot distinguish peptide effect from placebo or concurrent interventions

Manually researched from reddit, youtube, x— theme weights are research estimates, not live counts; aggregated & de-identified. No individual posts, quotes, or usernames are ever shown.

Relative research / market volume — populated once the activity stream is wired

Inline tooltips for lyophilized, RUO, EU/mg, SPPS, 503A and more.

Toggle plain-language ↔ scientific in the header.

• How to read a COA
• Free base vs acetate
• Understanding evidence grades

D-retro-inverso peptide designed to disrupt the FOXO4–p53 interaction in senescent cells, studied preclinically as a selective senolytic agent. Approximately 17 articles are indexed (literature last scanned 2026-05-29). US regulatory status: Research use only; not FDA-approved; not on FDA Category 2 bulk drug substances list. Research use only.

Emitted as JSON-LD: ChemicalSubstance · BreadcrumbList · FAQPage.

• Price-drop & back-in-stock alerts
• Regulatory-change email digest
• Print / share this datasheet