FOXO4-DRI (FOX-04)
D-retro-inverso FOXO4 / p53 interaction blocker · senolytic peptide
Overview
FOXO4-DRI (also called FOXO4-D-Retro-Inverso, FOX04, or FOX04-DRI) is a 29-amino-acid D-retro-inverso peptide designed to disrupt the FOXO4-p53 protein-protein interaction inside senescent cells. The D-retro-inverso architecture (using D-amino-acids in reversed sequence order) creates a peptide that is highly resistant to protease degradation while retaining the binding-interface topology of the natural L-peptide, a design strategy that dramatically extends the molecule's intracellular half-life. Originally described by Peter de Keizer's group at the University of Groningen in 2017, FOXO4-DRI became one of the most prominent published senolytic peptides, demonstrating selective induction of apoptosis in senescent cells in multiple aging and disease models. Lyochem supplies FOXO4-DRI as a lyophilized powder at ≥99.0% HPLC purity. The D-amino-acid synthesis is more demanding than typical L-peptide SPPS, D-Fmoc amino-acid building blocks cost substantially more than the L-amino-acid equivalents, which is the primary driver of FOXO4-DRI's higher per-mg pricing relative to similarly-sized L-peptides. The analytical packet covers peak-integration HPLC, mass spec confirming molecular weight, and on-request sequence verification by LC-MS/MS. Standard 2 mg and 10 mg fill sizes match typical senescence-research aliquot scales.
Who buys this, and why
Longevity-class peptides — Epitalon, FoxO4-DRI, PNC-27 — ship to research labs studying telomere maintenance, senescence-clearance, and tumour-suppressor pathways. The chemistry is well-behaved but solution stability matters: Epitalon and FoxO4-DRI both prefer chelator-free water and storage at −20 °C protected from light. For chronic-exposure in vivo work, request bacterial-endotoxin testing on the specific lot at quote stage.
Primary buyer fit: academic and contract research laboratories.
Specifications
- CAS
- 2460055-10-9
- Purity (HPLC)
- ≥ 99.0%
- Common vial sizes
- 2 mg, 10 mg
- MOQ
- On request
- Lead time
- 14–21 days
- Storage
- -20°C, protect from light
Documentation available on request
- Lot-specific Certificate of Analysis (CoA)
- RP-HPLC chromatogram with peak integration
- ESI-MS identity confirmation (±0.5 Da)
- Sequence verification by LC-MS/MS
- Water content by Karl Fischer
- SDS / MSDS
- Oxidative-stability series for solution work
- Stability at −20 °C across 12 months
- Solubility in chelator-free water + PBS
Regulatory note
Sold for Research Use Only under the receiving laboratory's institutional and jurisdictional regulations. Not a finished dosage form, not labelled for human administration, not for in-vitro diagnostic use. Chronic-exposure in vivo work should specify the additional analytical readouts needed (endotoxin, microbial limits, stability series) at quote stage.
Frequently asked questions
What does 'D-retro-inverso' mean and why is it used for FOXO4-DRI?▾
A D-retro-inverso (DRI) peptide reverses two things relative to the natural L-peptide: the chirality of every amino acid (D instead of L), and the sequence order (C-to-N instead of N-to-C). The combined transformation preserves the overall side-chain topology and binding-interface geometry while making the molecule unrecognizable to natural proteases, which cleave specifically at L-peptide bonds in N-to-C-reading order. The practical consequence for FOXO4-DRI is dramatically extended intracellular half-life (hours to days versus minutes for the natural L-peptide), which is essential for a research tool that needs sustained intracellular concentration to interfere with a protein-protein interaction.
What's the typical research context for FOXO4-DRI?▾
FOXO4-DRI is used as a research tool for selective induction of apoptosis in senescent cells (senolytic activity). The mechanism centers on disrupting the FOXO4-p53 nuclear interaction that senescent cells use to escape p53-mediated apoptosis; when the interaction is blocked, p53 redirects to mitochondria and triggers cell death selectively in senescent (but not proliferating) cells. The peptide has been studied in aging models, fibrosis models, cardiovascular disease, and as a hair-loss intervention in published research. It is a research tool only, not approved for any clinical indication.
Related peptides