FOXO4-DRI 10mg

FOXO4-DRI 10mg

At a Glance

• Peptide Type: Synthetic 46-residue D-retro-inverso peptide
• Primary Research Areas: Cellular senescence, senolytics, apoptosis, ageing research
• Mechanism of Interest: Competitive disruption of the FOXO4 to p53 interaction
• Structural Features: All D-amino acids in reversed sequence order for protease resistance, plus a TAT-derived cell-penetrating segment

Overview

FOXO4-DRI is a synthetic peptide of 46 residues, built entirely from D-amino acids and assembled in reverse order relative to its parent sequence. The name states the construction directly: D-Retro-Inverso. It was developed during work on cellular senescence, where researchers sought a way to interfere with a specific protein interaction that appears to keep senescent cells alive. FOXO4-DRI has since become one of the reference compounds in senolytic research, studied both for its biological target and as a well-documented example of how peptides can be engineered to reach targets inside the cell.

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Scientific Background

Senescent cells present an unusual problem. They have permanently stopped dividing yet do not die, remaining metabolically active in tissue and releasing signalling molecules into their surroundings. They accumulate with age. Interest in them grew sharply once it became clear that they are not inert passengers but active participants in how tissue behaves over time, and the field now extends across ageing research, inflammatory signalling and extracellular matrix biology.

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Mechanism of Interest

The mechanism under investigation concerns two proteins: FOXO4, a forkhead box transcription factor, and p53, one of the most studied regulators in cell biology. In healthy cells p53 can direct a damaged cell towards apoptosis. Senescent cells contain active p53 yet do not follow that instruction. One explanation is that elevated FOXO4 binds p53 and holds it in the nucleus, suppressing the apoptotic programme. FOXO4-DRI reproduces the region of FOXO4 that contacts p53 and competes for the same binding surface, acting as a decoy. The idea is scientifically interesting because it reframes senescence as an actively maintained state rather than a terminal one, which makes it an experimental lever.

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Research Focus Areas

1. Cellular Senescence. FOXO4-DRI is used to probe why a cell containing an active death signal does not act on it, and what happens when the proposed suppression of that signal is interrupted.
2. Selectivity. The central question in senolytic research is what distinguishes senescent from healthy cells. The proposed answer here rests on the internal state of the cell rather than a targeting address on the molecule, and investigations continue into where the boundaries of that distinction lie.
3. Senescence-Associated Secretory Phenotype. Work has examined how the secretory environment of a tissue or culture changes when senescent cells are cleared, with attention on inflammatory mediators and matrix metalloproteinase activity.
4. Retro-Inverso Peptide Design. Reversing both sequence order and residue chirality returns the side chains to approximately their original spatial positions while making the peptide resistant to proteolysis. FOXO4-DRI is one of the most cited demonstrations of this approach.
5. Cell Penetration and Delivery. A TAT-derived cell-penetrating segment gives the construct a strongly cationic character. Uptake routes, endosomal escape and cell-type variation remain active questions.

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Technical Details

• Synonyms: FOXO4 D-Retro-Inverso peptide, FOXO4 DRI, Proxofim
• Modified Single-Letter Sequence: D-(LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRPPPRRRQRRKKRG). All 46 residues are D-amino acids in retro-inverso orientation.
• IUPAC Condensed: D-(Leu-Thr-Leu-Arg-Lys-Glu-Pro-Ala-Ser-Glu-Ile-Ala-Gln-Ser-Ile-Leu-Glu-Ala-Tyr-Ser-Gln-Asn-Gly-Trp-Ala-Asn-Arg-Arg-Ser-Gly-Gly-Lys-Arg-Pro-Pro-Pro-Arg-Arg-Arg-Gln-Arg-Arg-Lys-Lys-Arg-Gly)
• Molecular Formula: C₂₂₈H₃₈₈N₈₆O₆₄
• Molecular Weight: 5358.06 g/mol (free peptide; commonly supplied as the acetate salt)
• CAS Number: 2460055-10-9
• PubChem CID: Not publicly available

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Stability and Storage

Store lyophilised peptide sealed and away from moisture at −20 °C. After reconstitution, aliquot the product to prevent repeated freeze–thaw cycles.
Reconstituted peptide may be stored at 4 °C for short-term use.
The lyophilised peptide remains stable until the expiry date when kept at −20 °C.

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Source and Reconstitution

Source: Chemical synthesis (solid-phase peptide synthesis)
Reconstitution: Reconstitute with Bacteriostatic Water

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Usage

Product is intended for laboratory research only.
FOXO4-DRI for sale at Pure Peptides UK is limited to scientific research and educational purposes.
Only purchase FOXO4-DRI if you are a licenced researcher.

Images for illustration purposes only.

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Conclusion

FOXO4-DRI holds attention for two distinct reasons. Biologically, it addresses one of the more striking puzzles in cell biology, namely why a cell containing an active death signal does not act on it. Structurally, it is a well-documented demonstration of how retro-inverso design and cell-penetrating sequences can be combined to reach a target that would otherwise be inaccessible. As senescence research continues to expand, FOXO4-DRI remains one of the reference compounds against which newer senolytic approaches are compared.

For research use only. Not approved for human or veterinary applications.