FOX04-DRI

FOXO4-DRI is a synthetic D-retro-inverso (DRI) senolytic peptide engineered to interfere with the FOXO4–p53 protein–protein interaction in senescent cells. The HPLC chromatogram and mass spectrometry trace shown above are the release data for the exact lot now shipping (batch APX-2026-0312-F) — not a stock graphic, not an archived summary, and not held behind an email request. The plot is the vial. This compound is supplied by Apex Laboratory strictly as a high-purity research reagent for in-vitro laboratory research and development applications, and is not approved for human consumption, veterinary use, or any therapeutic application.

Compound Overview

FOXO4-DRI is built on the core interface sequence that FOXO4 uses to dock onto p53, but it is assembled entirely from D-amino acids arranged in reversed sequence order — the defining feature of a retro-inverso peptide. Reversing the backbone direction while inverting each residue’s chirality preserves the overall topology of the original side-chain presentation, so the molecule can still recognise its target surface, yet the unnatural D-backbone resists cleavage by endogenous L-specific proteases. That protease resistance is what makes a DRI design attractive as a stable laboratory probe of a transient protein interaction.

Mechanistically, the peptide acts as an interaction inhibitor rather than an enzyme inhibitor. In senescent cells, the transcription factor FOXO4 is up-regulated and sequesters p53 in the nucleus, restraining the apoptotic program that p53 would otherwise drive. By occupying the FOXO4 docking interface, FOXO4-DRI displaces p53 from FOXO4 in model systems, allowing p53 to relocate and re-engage its pro-apoptotic targets. Because non-senescent cells carry comparatively little FOXO4 activity at this interface, the displacement is reported to bias toward senescent populations — the basis for classifying the molecule as a senolytic research tool. This places FOXO4-DRI in a distinct mechanistic category from telomerase-pathway bioregulators such as Epithalon or mitochondrial-targeted peptides such as SS-31: instead of supporting cellular maintenance, it is studied for the selective removal of cells that have already entered senescence.

Research Background & Published Literature

FOXO4-DRI entered the literature through the work of Baar and colleagues at Erasmus University Medical Center, published in Cell in 2017. That study characterised the FOXO4–p53 axis in senescent cells and reported that interfering with the interaction triggered targeted apoptosis of senescent populations in cultured cells and in aged mouse models, establishing the peptide as a reference tool for the emerging senolytics field. Since then it has been used widely as a positive control and mechanistic probe in studies of cellular senescence, the senescence-associated secretory phenotype (SASP), and p53-dependent apoptosis. As a designed peptide it carries no marketing-authorisation history; published interest remains entirely preclinical and in-vitro.

Researchers reviewing the published record for this compound can begin with the foundational citation below and broaden the search through the indexed literature on the FOXO4–p53 interaction and DRI peptide chemistry:

• Baar et al. (2017) — Targeted apoptosis of senescent cells via the FOXO4-DRI senolytic peptide (Cell)
• PubMed — FOXO4, p53 and senescence peptide literature
• PubChem — FOXO4-DRI structural and identifier records

Technical Specifications

Storage, Handling & Stability

As a large, multi-residue peptide, FOXO4-DRI is most stable in its lyophilized state. Store the sealed vial at -20°C — or colder for extended archival — protected from light and moisture. The D-amino-acid backbone confers good resistance to enzymatic degradation, but it does not protect against the physical instability common to peptides of this size in solution, so reconstituted material should be treated as time-limited. After reconstitution in sterile diluent, hold working solution at 2–8°C, aliquot before first use, and avoid repeated freeze–thaw cycles that can drive aggregation in a ~5.4 kDa peptide.

• Allow the sealed vial to reach room temperature before opening to limit condensation onto the dry cake.
• Reconstitute gently down the vial wall rather than directly onto the lyophilisate, and swirl — do not vortex — to reduce shear and foaming.
• Split reconstituted material into single-experiment aliquots so the bulk stock is never thawed more than once.
• Label each aliquot with compound name, concentration, reconstitution date, and operator initials for full lot traceability.

Quality Assurance & Analytical Verification

Every FOXO4-DRI lot is released against a dual-verification protocol before it reaches inventory: reversed-phase High-Performance Liquid Chromatography to establish chromatographic purity, and Mass Spectrometry to confirm molecular identity. The data displayed at the top of this page is the actual release record for the shipping lot — batch APX-2026-0312-F, tested 2026-03-12 by analyst K. Norwood, returning 99.74% purity at a 19.0-minute retention time.

At roughly 5,358 Da, FOXO4-DRI sits well above the size range where a single protonated molecular ion is diagnostic, so identity is confirmed from a multiply-charged electrospray (ESI+) envelope rather than one peak. The deconvoluted mass found this lot, 5358.45, agrees with the expected 5358.05 to within the tolerance appropriate for a peptide of this molecular weight, confirming intact assembly of the full D-retro-inverso sequence. For the rationale behind reading several charge states together, see our guide to mass spectrometry for peptide verification; for how the numbers on the panel above are derived, see HPLC and MS purity testing and how to read a Certificate of Analysis. Prior-lot records are archived in our Lab Verified COA library.

Frequently Asked Questions

What does the “DRI” in FOXO4-DRI mean, and why does it matter?

DRI stands for D-retro-inverso. The peptide is synthesised from D-amino acids assembled in reverse sequence order relative to the natural FOXO4 interface segment. This combination approximately preserves the spatial arrangement of the side chains that recognise the target while replacing the natural L-backbone with a mirror-image D-backbone that endogenous proteases do not readily cleave — giving the molecule far greater metabolic stability than a conventional L-peptide of the same sequence in laboratory model systems.

How does FOXO4-DRI act on the FOXO4–p53 interaction?

In senescent cells, FOXO4 holds p53 in the nucleus and suppresses p53-driven apoptosis. FOXO4-DRI is studied as an interaction inhibitor that competes for the FOXO4 docking surface, displacing p53 in cell-model experiments and allowing the apoptotic program to proceed. Because the relevant FOXO4 activity is concentrated in senescent populations, the displacement is reported to bias toward those cells in published preclinical work.

What molecular weight and formula should the COA show?

FOXO4-DRI has the molecular formula C₂₂₈H₃₈₈N₈₆O₆₄ and an expected monoisotopic/average mass near 5358.05 g/mol. The current lot returned a mass-spectrometry value of 5358.45 and 99.74% chromatographic purity — both visible on the panel at the top of this page. If a supplier quotes a markedly lower figure such as “~4800,” that does not correspond to the full DRI sequence verified here.

How is FOXO4-DRI different from other longevity-focused research peptides?

Bioregulators such as Epithalon and mitochondrial peptides such as MOTS-c are studied for cellular maintenance and stress-response signalling. FOXO4-DRI works at the opposite end of that spectrum: it is a senolytic candidate, investigated for the selective clearance of cells that have already become senescent rather than for supporting healthy cells. See the longevity and bioregulator pillar guide for how these mechanisms compare.

Is this product approved for human use?

No. All compounds sold by Apex Laboratory are classified as chemical research reagents intended strictly for in-vitro laboratory research. They are not approved for human consumption, veterinary use, or any therapeutic application. FOXO4-DRI is an investigational research peptide with no marketing authorisation from the FDA or any other regulatory authority for any indication. Purchasers who imply intended bodily use will have their orders cancelled and their accounts permanently suspended.

Is bulk ordering available?

Yes. For larger quantities, custom packaging, or recurring supply agreements, contact our team through the contact page with the compound name, desired quantity, preferred size format, and your target delivery timeline. Volume pricing is available for qualifying institutional and repeat orders.

Related Research Compounds

Laboratories studying cellular senescence, the FOXO4–p53 axis, and longevity-pathway pharmacology often pair FOXO4-DRI with complementary reagents available from Apex Laboratory: Epithalon (telomerase-pathway bioregulator), SS-31 (cardiolipin-targeted mitochondrial peptide), MOTS-c (mitochondrial-derived peptide), and 5-Amino-1MQ (NNMT inhibitor). Browse the full selection in the Apex Laboratory research catalog.

Shipping, Packaging & Delivery

Orders confirmed before 2:00 PM Eastern Time on a business day leave the same day by tracked US domestic carriers. Each FOXO4-DRI vial is packed in insulated, temperature-conscious packaging chosen to protect the lyophilised peptide through transit. Move the vial to -20°C storage as soon as it arrives. If your protocol is time-critical or you need a specific delivery window, reach out before ordering and we will coordinate the dispatch timing around your bench schedule.

Research Use Disclaimer

For in-vitro research use only. Not for human consumption. All products sold by Apex Laboratory — including FOXO4-DRI — are intended exclusively for qualified researchers, accredited laboratories, and educational institutions. FOXO4-DRI is an investigational research peptide that has not received marketing authorisation from the FDA or any other regulatory body for any use. Purchasers assume full responsibility for safe handling, proper storage, and compliance with all applicable federal, state, and local laws, regulations, and institutional policies governing the purchase and use of chemical research reagents.

Research guide: See FOXO4-DRI Research Guide: Senolytic Peptide and the FOXO4-p53 Axis for mechanism, handling, and published study context. Research-use only; not for human or veterinary use.