FOXO4-DRI

FOXO4-DRI Mechanism of Action

FOXO4-DRI was developed as a synthetic peptide designed to investigate the protein–protein interaction between FOXO4 and p53. FOXO4 is a member of the forkhead box O (FOXO) family of transcription factors and contains a region capable of interacting with p53. Research has identified the FOXO4–p53 interaction as a molecular feature of cell-cycle arrest models, providing a basis for studying how protein interactions influence cellular behavior. [1]

D-Retro-Inverso Peptide Design

The name FOXO4-DRI refers to its D-retro-inverso design. In this approach, the peptide uses D-amino acids and a reversed sequence orientation relative to the corresponding parent peptide segment. This combination can preserve aspects of the spatial arrangement of amino acid side chains while producing a peptide with different backbone characteristics and resistance to enzymatic degradation. [2] FOXO4-DRI was designed using this approach to produce a peptide capable of interacting with the FOXO4–p53 system.

FOXO4–p53 Protein Interaction

FOXO4 can interact with p53 through specific molecular contacts involving regions of both proteins. Experimental research has investigated FOXO4-DRI as a competitive peptide designed to interfere with this protein–protein interaction. More recent structural research has characterized direct binding between FOXO4-DRI and the transactivation domain of p53, providing molecular evidence for the interaction between the peptide and its target region. [3]

Cell-Cycle Arrest Research

The FOXO4–p53 interaction has been studied in the context of cell-cycle arrest, a state in which cells undergo persistent changes in proliferation and cellular function. Experimental studies have used FOXO4-DRI as a molecular tool for investigating this interaction in cell-cycle-arrested cell models. [4]

These findings provide a research framework for examining the relationship between FOXO4, p53, protein–protein interactions, and arrest-associated cellular processes.

FOXO4-DRI Research Applications

FOXO4-DRI has been investigated primarily as a molecular research tool for studying protein–protein interactions, cell-cycle arrest, and p53-related signaling. Its defined D-retro-inverso structure makes it particularly relevant to experiments examining how modified peptides interact with intracellular protein targets.

FOXO4–p53 Protein–Protein Interaction Research

One of the principal research applications of FOXO4-DRI is the study of the FOXO4–p53 interaction. Experimental work has used the peptide to investigate whether disrupting this protein–protein interaction changes the behavior of cell-cycle-arrested cell models. More recent structural studies have examined the molecular contacts between FOXO4-DRI and the p53 transactivation domain, providing additional information about the interaction at the molecular level. [5]

Cell-Cycle Arrest Models

FOXO4-DRI has been investigated in experimental models of cell-cycle arrest. Researchers can use these models to examine relationships between arrest-associated cellular states, FOXO4, p53, and programmed cell death. The foundational studies of FOXO4-DRI reported experimental effects in cell-cycle-arrested cell populations, establishing the peptide as a tool for investigating the molecular biology of cell-cycle arrest. [4] [7]

p53 Signaling Research

Because FOXO4-DRI interacts with a region of p53 involved in protein recognition, it can be used in research examining p53-related molecular pathways. Experimental studies can investigate protein localization, protein–protein interactions, and changes in cellular signaling associated with disrupting specific molecular contacts involving p53. [6]

Structural and Biophysical Research

The defined peptide structure of FOXO4-DRI also makes it relevant to structural biology and biophysical research. Studies can examine peptide–protein binding, molecular recognition, conformational characteristics, and the interactions between FOXO4-DRI and target protein domains using appropriate experimental techniques.

D-Retro-Inverso Peptide Research

FOXO4-DRI provides a research model for investigating D-retro-inverso peptide design. Researchers can examine how reversing sequence orientation and replacing L-amino acids with D-amino acids affects peptide structure, molecular recognition, and resistance to enzymatic degradation. Such work contributes to broader research into chemically modified peptides and peptide-based molecular probes.

FOXO4-DRI Compared With Related Research Materials

FOXO4-DRI is a specialized peptide research tool rather than a direct substitute for the full-length FOXO4 protein or other FOXO4-derived research constructs. Comparing these materials primarily involves their molecular structure, composition, and intended research purpose.

Note: All materials listed for laboratory research use only.

FOXO4-DRI vs. Native FOXO4

FOXO4-DRI should not be confused with the native FOXO4 protein. FOXO4 is a full-length transcription factor containing multiple functional domains, whereas FOXO4-DRI is a much smaller synthetic peptide designed from a FOXO4-derived region. Its D-retro-inverso configuration also means that it is not simply a fragment of native FOXO4. Instead, it is a chemically modified research construct designed to reproduce specific molecular recognition properties of the parent sequence.

Related Peptides in Cellular and Tissue Research

FOXO4-DRI represents one research approach for studying cell-cycle arrest and FOXO4–p53 protein interactions. Other research peptides address different aspects of cellular and tissue biology and can provide useful points of comparison when designing experimental models. For example:

• Body Protection Compound 157 (Pentadecapeptide) (BPC-157) is a synthetic pentadecapeptide investigated primarily in preclinical research involving cellular signaling, vascular biology, and tissue-repair models.

• Thymosin Beta-4 Fragment (TB-500) is associated with research into thymosin beta-4-related biology, including actin dynamics, cell migration, and tissue organization.

• Glycyl-Histidyl-Lysine-Copper(II) (GHK-Cu) is a copper-binding tripeptide studied in research involving extracellular matrix biology, collagen-related processes, gene expression, and cellular signaling.

These compounds are not molecular equivalents of FOXO4-DRI and should not be assumed to produce the same experimental effects. Their inclusion here reflects their relevance to broader research into cellular, tissue, and regenerative biology rather than a shared mechanism or established application in cell-cycle arrest.

For researchers working across related areas, exploring these peptides alongside FOXO4-DRI can provide additional context for studying distinct molecular pathways and experimental systems.

Storage & Laboratory Handling

FOXO4-DRI is supplied as a lyophilized research material. Proper storage and handling can help minimize moisture exposure, temperature-related degradation, and unnecessary changes to the material.

• Keep the vial sealed: Maintain the original sealed container until the material is required for laboratory work.

• Control temperature: Store the lyophilized material according to Bluum Peptides' product-specific storage instructions.

• Protect from moisture: Keep the material dry and minimize exposure to atmospheric moisture.

• Protect from light: Store away from direct sunlight and prolonged exposure to strong laboratory lighting.

• Minimize temperature cycling: Avoid unnecessary changes between storage temperatures and repeated freeze-thaw exposure.

• Minimize condensation: When removing cold material from storage, allow the sealed vial to reach an appropriate handling temperature before opening to reduce potential condensation exposure.

• Maintain batch traceability: Keep the vial, lot number, Certificate of Analysis, and laboratory records together so experimental material can be traced to its tested batch.

• Follow institutional protocols: Institutional, laboratory-specific, and study-specific SOPs should be applied alongside the manufacturer's product instructions.

Published research does not establish a universal shelf life or stability period for FOXO4-DRI under all storage conditions. Researchers should therefore rely on the manufacturer's product documentation, batch-specific information, and validated laboratory procedures rather than assuming a fixed stability period.

FOXO4-DRI is intended for laboratory research only.

Certificate of Analysis & Quality Assurance

FOXO4-DRI from Bluum Peptides is tested for research-grade quality and purity. Every new batch of FOXO4-DRI is tested through independent third-party laboratories for analytical parameters that include purity, identity, sterility, endotoxins, and heavy metals, among others. Batch-specific Certificates of Analysis (COA) are provided for verification.

The Bluum Peptides Lab Reports page can also be used to access available certificates and trace each certificate to the testing laboratory.

Frequently Asked Questions

1. What is FOXO4-DRI? FOXO4-DRI is a synthetic D-retro-inverso peptide derived from a region of the FOXO4 protein. It was developed as a molecular research tool for investigating the interaction between FOXO4 and the tumor suppressor protein p53. Research has examined FOXO4-DRI in cell-cycle arrest models, protein–protein interaction studies, p53 localization experiments, and structural studies of peptide–protein binding.

2. What does DRI mean in FOXO4-DRI? DRI stands for D-retro-inverso. This describes a peptide design in which the amino acid sequence is reversed and the residues are represented in the D-configuration. FOXO4-DRI uses this structural approach to create a synthetic peptide based on a FOXO4-derived sequence while producing a distinct molecular architecture from the corresponding native peptide region.

3. How does FOXO4-DRI interact with the FOXO4-p53 pathway? FOXO4-DRI has been investigated in relation to the protein–protein interaction between FOXO4 and p53. Structural research published in 2025 found that FOXO4-DRI interacts directly with the disordered TAD2 region of the p53 transactivation domain, forming a transiently structured complex. The study also found that both the FOXO4-derived portion and the peptide's cationic cell-permeability sequence contribute to the interaction.

These findings provide a molecular basis for studying FOXO4–p53 interaction and related signaling mechanisms in experimental systems.

4. What is FOXO4-DRI used for in research? FOXO4-DRI is used as a research material in experimental studies involving FOXO4–p53 protein–protein interactions, cell-cycle arrest models, p53 localization, and peptide-mediated pathway modulation. Researchers have also investigated its molecular interactions using structural and biophysical techniques, including studies of peptide–protein binding.

The specific experimental application depends on the research model and study design.

5. What is the difference between FOXO4 and FOXO4-DRI? FOXO4 is a naturally occurring transcription factor and full-length protein. FOXO4-DRI is a synthetic peptide derived from a specific region of FOXO4 and modified using a D-retro-inverso design.

They therefore differ substantially in size, structure, amino acid configuration, and experimental role. FOXO4-DRI is studied as a defined peptide molecular probe, whereas native FOXO4 is a full-length cellular protein involved in transcriptional regulation and protein–protein interactions.

6. What is the FOXO4-DRI sequence and molecular weight? Bluum Peptides lists FOXO4-DRI as a 46-residue peptide composed entirely of D-amino acids. The listed sequence is:

H-ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg-OH

The molecular formula is C228H388N86O64, with a listed molecular weight of approximately 5,358.06 g/mol. The compound is also listed under names including FOXO4 D-Retro-Inverso and FOXO4 DRI.

7. How is FOXO4-DRI tested for purity and identity? FOXO4-DRI from Bluum Peptides is a research product tested by independent labs through analytical testing standards for parameters such as purity, identity, sterility, and endotoxins. Results are documented in batch-specific Certificates of Analysis (COAs) provided on the product page.

8. Where can I obtain FOXO4-DRI for laboratory research? FOXO4-DRI is available from Bluum Peptides as a 10 mg lyophilized research material, tested by independent third-party laboratories for quality and purity standards. This material is supplied strictly for laboratory research use only.

Scientific References

1. Liu W, Li Y, Luo B. Current perspective on the regulation of FOXO4 and its role in disease progression. Cell Mol Life Sci. 2020 Feb;77(4):651-663. https://pubmed.ncbi.nlm.nih.gov/31529218/

2. Huang Y, He Y, Makarcyzk MJ, Lin H. Front Bioeng Biotechnol. 2021 Apr 29;9:677576. https://pubmed.ncbi.nlm.nih.gov/33996787/

3. Bourgeois B, Spreitzer E, Platero-Rochart D, Paar M, Zhou Q, Usluer S, de Keizer PLJ, Burgering BMT, Sánchez-Murcia PA, Madl T. Nat Commun. 2025 Jul 1;16(1):5672. https://pubmed.ncbi.nlm.nih.gov/40593617/

4. Le HH, Cinaroglu SS, Manalo EC, Ors A, Gomes MM, Duan Sahbaz B, Bonic K, Origel Marmolejo CA, Quentel A, Plaut JS, Kawashima TE, Ozdemir ES, Malhotra SV, Ahiska Y, Sezerman U, Bayram Akcapinar G, Saldivar JC, Timucin E, Fischer JM. EBioMedicine. 2021 Nov;73:103646. https://pubmed.ncbi.nlm.nih.gov/34689087/

5. Tripathi U, Chaib S, Gerdes EOW, Hogan KA, Zhu Y. EBioMedicine. 2021 Dec;74:103693. https://pubmed.ncbi.nlm.nih.gov/34768086/

6. Mandal R, Kohoutova K, Petrvalska O, Horvath M, Srb P, Veverka V, Obsilova V, Obsil T. FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA. Protein Sci. 2022 May;31(5):e4287. https://pubmed.ncbi.nlm.nih.gov/35481640/

7. Baar MP, Brandt RM, Putavet DA, et al. Cell. 2017 Mar 23;169(1):132-147.e16. https://www.cell.com/cell/fulltext/S0092-8674(17)30246-5