Foxo4 Peptide

FOXO4 peptide are a class of protein–protein interaction (PPI)–interfering peptides designed on the FOXO4–p53 interaction interface, used as research raw materials for the selective elimination of senescent cells.

The design rationale is to competitively block FOXO4–p53 binding, removing the survival dependence of senescent cells on this complex; this promotes p53 export from the nucleus and activates mitochondrial apoptotic signaling, thereby achieving selective killing of senescent cells.

Shaanxi Medibridge supplies FOXO4 raw powder at no less than 99.12% purity, verified by HPLC/MS. As a peptide raw material supplier operating under GMP Management Standards, we ensure consistent quality, full batch traceability, and dependable lead times. Each lot ships with a COA and complete documentation. Custom specifications and scale‑up are available on request. Reliable global logistics and responsive technical support help keep your research moving.

1. Purity ≥ 99.12%, HPLC/MS dual release.

2. GMP managed system production, high batch-to-batch consistency, full traceability.

3. Complete quality documentation: CoA, HPLC/MS chromatograms, residual solvent and salt type reports.

4. Flexible customization: Sequence/salt type (TFA and acetate removed), scale-up.

5. Stable delivery: Lyophilized powder, low-temperature and light-protected packaging, controllable delivery time.

6. Professional support: Dissolution and preparation guidelines, application consultation, and after-sales service.

Upstream triggers and FOXO4 accumulation

Senescence-associated stresses (DNA damage, telomere shortening, oxidative stress) activate the DDR→p53–p21 axis and maintain growth arrest. In parallel, FOXO4 expression/stability and nuclear localization are upregulated, with sustained residency in senescent cells, setting the stage for subsequent stable complex formation with p53.

 

Biological role of the FOXO4–p53 complex

In senescent cells, FOXO4 forms a complex with p53 that promotes p53's nuclear retention, steering it toward a transcriptional program that sustains arrest and survival (e.g., p21) while suppressing its mitochondrial pro‑apoptotic function. Functionally, this complex is a support point that preserves the senescent steady state and prevents apoptosis.

Binding site and conformational logic of the interfering peptide

The FOXO4 peptide is derived from the key FOXO4–p53 contact region and uses a D‑retro‑inverso (DRI) design to preserve side‑chain orientation while markedly enhancing resistance to proteolysis. It competitively occupies the binding interface, thereby weakening or dismantling the endogenous FOXO4–p53 complex.

 

Initiation of the mitochondrial pathway

Once released from nuclear retention, p53 engages BCL‑2 family members at the cytosol/mitochondrial surface, triggering conformational activation of BAX/BAK and mitochondrial outer membrane permeabilization (MOMP). Cytochrome c is then released and the caspase cascade is activated, yielding selective apoptosis of senescent cells.

D‑retro‑inverso (DRI) strategy

The peptide sequence is reversed and built from D‑amino acids; side‑chain spatial orientation mimics the native L‑peptide, while markedly increasing resistance to proteolysis and in vivo persistence.

 

Cellular entry

Commonly achieved by fusing a CPP at the N‑ or C‑terminus (e.g., TAT‑type or other polybasic segments) to enhance endocytosis/transport efficiency.

 

Solubility and isoelectric point

Enriched in basic residues, typically weakly basic with moderate hydrophilicity; most lots dissolve in sterile water, PBS, or buffers containing a small amount of DMSO (a small amount of polar co‑solvent may be added if needed).

 

Formulation

Typically supplied as a lyophilized powder, dosed by net peptide content; commonly provided as the TFA or acetate salt (excess TFA may increase background cytotoxicity-prefer the acetate salt or perform TFA removal).

This outline is provided solely for research/academic exchange.

Controls

Matched non‑senescent counterpart cells to verify selectivity rather than general cytotoxicity.

Scrambled‑sequence peptide as a negative control; match net peptide content and salt form.

p53‑status controls: p53 inhibitor, knockdown, or mutant models to demonstrate p53 dependence.

CPP‑only control to assess any effects intrinsic to the cell‑penetrating segment.

Dose and timing optimization

Test a 0.5–20 μM concentration range and a 24–96 h time course to identify the widest selectivity window (strong killing of senescent cells with minimal impact on non‑senescent cells).

Data interpretation

Use senolysis selectivity as the primary endpoint; calculate a selectivity index (e.g., non‑senescent viability/senescent viability under identical conditions, or an EC50 ratio).

Do not conclude from SA‑β‑gal alone; include apoptosis readouts and SASP markers at minimum.

If only transient SASP changes are seen, consider sampling time points carefully (early apoptotic stress can briefly elevate inflammatory factors before they decline).

Need a dependable manufacturer for GLP‑1/Dual (GLP‑1/GIP) and FOXO4 peptide? We operate under GMP management, supplying research‑use‑only materials with transparent COAs, strong lot‑to‑lot consistency, and prompt technical support. For quotes, lead times, or custom specifications, contact hi@medibridgeapi.com or WhatsApp +44 07548632075.

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