D-Retro-Inverso Peptide · FOXO4-p53 Interaction Research
FOXO4-DRI
Research Compound
A modified peptide using the D-amino acid retro-inverso strategy, derived from the FOXO4 transcription factor sequence. Designed for preclinical research into FOXO4-p53 protein-protein interaction, cellular senescence pathways, and apoptosis signaling in in vitro models.
Compound Specs
Compound Overview
What Is FOXO4-DRI?
A deep-dive into the peptide design, molecular target, and research background behind one of the most structurally sophisticated compounds in the senescence research field.
D-Retro-Inverso Strategy
FOXO4-DRI employs the D-retro-inverso (DRI) peptide strategy: the amino acid sequence is reversed (retro) and all residues are substituted with their D-enantiomers (inverso). This dual modification results in a peptide that presents a near-identical topological surface to the native L-amino acid sequence — preserving target recognition — while dramatically enhancing resistance to endogenous protease degradation. The result is a structurally stable research tool for cell-based and preclinical work.
FOXO4 Transcription Factor
FOXO4 (Forkhead Box O4) is a member of the Forkhead transcription factor family, involved in the regulation of apoptosis, cell cycle arrest, and stress response. Preclinical research has investigated its differential expression and function in senescent versus healthy cells. FOXO4 has been examined in the context of senescent cell survival signaling, particularly its interaction with p53 at the nuclear level in cell models.
p53 Protein Interaction Research
Published research has examined whether FOXO4 interacts with p53 within senescent cells to influence p53 nuclear localization and apoptotic signaling. The research hypothesis investigated in preclinical models centers on whether disrupting the FOXO4-p53 protein-protein interaction can affect p53 cytoplasmic translocation and downstream apoptosis pathway activity specifically in senescent cell populations in vitro and in animal models. This remains an active area of p53 pathway research.
de Keizer 2017 — Utrecht University
The FOXO4-DRI compound was developed by Peter de Keizer and colleagues at Utrecht University Medical Center. The foundational research was published in Cell in 2017, investigating the FOXO4-p53 interaction hypothesis in preclinical cell models and animal models. This work established FOXO4-DRI as a research tool for studying senescent cell biology and the molecular underpinnings of FOXO4-p53 signaling — representing a significant methodological contribution to cellular senescence research.
Molecular & Classification Data
| Full Name | FOXO4 D-Retro-Inverso Peptide (FOXO4-DRI) |
| Peptide Class | D-retro-inverso modified research peptide |
| Derived From | FOXO4 protein sequence (Forkhead Box O4 transcription factor) |
| Modification Strategy | All-D amino acid substitution + reversed sequence (retro) |
| Molecular Weight (approx.) | ~4,600 Da |
| CAS Number | N/A — research compound, no established CAS registry |
| Research Classification | Frontier-tier research compound; cellular senescence pathway research tool |
| Research Origin | de Keizer et al., Utrecht University, published in Cell, 2017 |
| Use Classification | For research use only — not for human use or therapeutic application |
Preclinical Research Areas
Research Background
Published research has examined FOXO4-DRI across five primary preclinical and cell model research areas. The following summaries reflect published and preclinical research only — not clinical findings or human data.
FOXO4-p53 Protein-Protein Interaction Research in Cell Models
Preclinical research has investigated the FOXO4-p53 protein-protein interaction within senescent cell populations in vitro. Research has examined the structural basis of this interaction and whether specific peptide sequences can disrupt the binding interface. Cell model studies have explored how this interaction may relate to p53 localization and senescent cell signaling dynamics.
Cellular Senescence Pathway Research
Published research has examined FOXO4's role in cellular senescence pathway regulation in vitro. Preclinical research has investigated the molecular mechanisms by which FOXO4 expression and activity may differ in senescent versus proliferating cells, providing a framework for understanding FOXO4-DRI's utility as a research tool in senescence pathway studies.
Apoptosis Induction Research in Senescent Cells In Vitro
Preclinical research has examined apoptosis pathway activity in senescent cell models following FOXO4-p53 interaction disruption in vitro. Published research has investigated whether specific molecular interventions affect caspase-3 activation and other apoptosis markers selectively in senescent versus healthy cell populations in cell culture and preclinical models.
p53 Nuclear Localization Research in Preclinical Models
Preclinical research has investigated p53 nuclear export and cytoplasmic localization in senescent cell models. Published research has examined whether modulating the FOXO4-p53 interaction influences p53's nuclear-cytoplasmic distribution — a key area of interest for understanding p53-mediated apoptosis signaling research in the context of cellular aging biology.
Senolytic Mechanism Research in Animal Models
Preclinical animal model research has investigated FOXO4-DRI as a research tool for studying senescent cell clearance mechanisms. Published research has examined physiological readouts in aged animal models following FOXO4-DRI research sample introduction, contributing to understanding of senolytic mechanism research and the biology of cellular senescence in vivo. This research remains in the preclinical phase.
Chemistry Explainer
What Is a D-Retro-Inverso Peptide?
Reversed Sequence
In the "retro" modification, the peptide's amino acid sequence is written and synthesized in reverse order — C-terminus to N-terminus. This inverts the directionality of the backbone while preserving residue identity.
D-Amino Acid Substitution
In the "inverso" modification, every natural L-amino acid is replaced with its D-enantiomer mirror image. D-amino acids are not recognized by most endogenous proteases, which are stereospecific for L-form substrates, conferring significant stability to enzymatic degradation.
Topological Surface Preservation
The dual DRI modification is elegant: the reversal of the backbone combined with the mirror-image residues results in a peptide whose overall side-chain topology closely resembles the original native sequence — enabling recognition of the same molecular targets while resisting proteolytic cleavage in biological research environments.
Enhanced Stability in Models
The protease resistance of DRI peptides makes them particularly useful as research tools in cell-based and animal model studies, where standard L-amino acid peptides may be rapidly degraded before producing measurable effects on the target pathway being investigated.
Sequence Labs Supply
FOXO4-DRI — 10 mg Vial
- 10 mg lyophilized powder per vial
- HPLC + Mass Spectrometry verified — dual confirmation on every batch
- ≥98% purity — independently verified by Krause Analytical
- COA available — Krause Analytical certificate on file
- Reviewed by Sabrina Runbeck, PA-C — licensed PA-C catalog review
- Finnrick Pulse supply chain verification
- Ships within 1–2 business days; discrete packaging
- For research use only — not for human use
Verified By
Quality Standards
Reconstitution Reference
Introducing Solvent to FOXO4-DRI
FOXO4-DRI is supplied as a lyophilized powder. The following reference is provided for qualified research use only. For research use only — not for human use.
Reconstitution Reference Steps
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1
Allow vial to reach ambient temperature before opening. Lyophilized peptides are sensitive to moisture condensation during cold-to-warm transitions.
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2
Prepare bacteriostatic water as the recommended solvent. FOXO4-DRI is generally water-soluble; bacteriostatic water is preferred for research sample longevity.
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3
Gentle warming may aid dissolution. FOXO4-DRI can be challenging to dissolve relative to many other research peptides. Warming the bacteriostatic water to approximately 37°C before introduction may facilitate reconstitution.
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4
Introduce solvent slowly against the vial wall. Add bacteriostatic water dropwise with gentle pressure rather than directly onto the lyophilized cake.
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5
Gently swirl — do not vortex. Vortexing can cause peptide aggregation. Gently roll or swirl the vial. Allow time; full dissolution may take several minutes for this compound.
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6
Store reconstituted research sample at 2–8°C and use within the timeframe appropriate for your research protocol. Avoid freeze-thaw cycles after reconstitution.
FOXO4-DRI is considered one of the more challenging research peptides to fully reconstitute due to its larger molecular weight (~4,600 Da) and modified D-amino acid structure. Researchers have noted that this research sample may require additional time, gentle warming, and patience to achieve full dissolution. If the solution appears slightly opaque after initial reconstitution, continue gentle swirling before assuming incomplete dissolution. Do not use heat above 40°C.
Solvent Options for Research
All reconstitution guidance is provided for qualified research informational purposes only. FOXO4-DRI supplied by Sequence Labs is for in vitro and preclinical research use only. Not for human use, consumption, or therapeutic application. Sequence Labs LLC makes no representations regarding the suitability of this compound for any specific research application. Researchers are responsible for all compliance with applicable laws and institutional guidelines.
Frequently Asked Questions
FOXO4-DRI Research Questions
Sequence Labs Research Supply
Source FOXO4-DRI for Your Research
FOXO4-DRI is a frontier research compound available in 10 mg HPLC + MS verified vials from Sequence Labs. Order directly from the products page or contact us for bulk pricing.