FOXO4-DRI¶

Identification¶

Property	Value
CAS Number	— (D-Retro-Inverso peptide)
Molecular Formula	—
Molecular Weight	~4,316.0 Da
Sequence	D-Retro-Inverso 47-mer (all D-amino acids, reversed sequence)
Amino Acid Count	47 (all D-amino acids, retro-inverso)
Appearance	White to off-white lyophilized powder
Purity Standard	≥99% by HPLC
Solubility	Soluble in sterile water or PBS
Storage	2–8°C, desiccated, protect from light

Category: Nootropic & Anti-Aging

Catalog SKU: PSH-FOXO4-5MG

Research Background¶

FOXO4-DRI (D-Retro-Inverso) is a modified peptide that disrupts the FOXO4-p53 interaction in senescent cells — a mechanism for targeted senescent cell clearance (senolysis). It represents a fundamentally different approach from signaling peptides: rather than modulating a pathway, it targets a specific protein-protein interaction. The D-Retro-Inverso modification (all D-amino acids, reversed sequence) makes the peptide essentially invisible to proteases, conferring dramatically extended half-life. Developed by the de Keizer lab, FOXO4-DRI is a landmark tool in cellular senescence research.

Key Mechanisms¶

Mechanism	Details
FOXO4-p53 Disruption	Competes with FOXO4 for p53 binding → releases nuclear p53 → triggers apoptosis
Senescent Cell Selectivity	Senescent cells have elevated FOXO4-p53 complexes — DRI selectively disrupts these
D-Retro-Inverso Design	All-D-amino acid, reversed sequence → complete protease resistance → extended half-life
BAX/BAK Activation	Released p53 → mitochondrial BAX/BAK → cytochrome c → caspase cascade → apoptosis

Research Focus Areas¶

Cellular Senescence¶

p53-mediated senescent cell apoptosis induction

Senolytic Research¶

Selective elimination of senescent cells without affecting proliferating cells

Aging Models¶

Age-related pathology reduction; healthspan extension in rodent models

Chemotherapy Protection¶

Doxorubicin-induced senescence and cardiotoxicity mitigation

Available Configurations¶

Configuration	Content	Best For
Standard Kit	5 mg × 10 vials	Senolytic research; evaluation
Bulk Kit	10 mg × 10 vials	Aging models; repeat orders
Custom	Custom mg × custom vials	OEM; private-label

Tiered Wholesale Pricing¶

Volume	Discount	For
1 kit	List price	Evaluation; competitive analysis
5+ kits	10% off	Initial portfolio expansion
20+ kits	20% off	Mid-size distributors
50+ kits	30% off	Regional distributors

Quality Specifications¶

Parameter	Method	Criterion
Purity	HPLC at 214 nm, C18 column	≥99.0% peak area
Identity (MW)	MALDI-TOF MS	~4,316.0 ± 2.0 Da
Appearance	Visual inspection	White to off-white powder
Chiral Purity	Chiral amino acid analysis	All D-amino acids confirmed
Residual Moisture	Karl Fischer	≤3%

Frequently Asked Questions¶

Q1: What is FOXO4-DRI and how does it work?¶

FOXO4-DRI is a 47-amino acid D-Retro-Inverso peptide that disrupts the FOXO4-p53 interaction in senescent cells. FOXO4 normally sequesters p53 in the nucleus of senescent cells, preventing apoptosis. DRI displaces FOXO4 → releases p53 → triggers mitochondrial apoptosis cascade → selectively eliminates senescent cells.

Q2: What does D-Retro-Inverso mean?¶

The peptide is synthesized from all D-amino acids (not natural L-form) in reversed sequence order. Result: same 3D side-chain topology as natural L-peptide but completely resistant to proteolytic degradation — proteases only recognize L-amino acids.

Q3: How does FOXO4-DRI selectively target senescent cells?¶

Senescent cells accumulate high FOXO4-p53 complexes as part of their anti-apoptotic survival program. DRI specifically disrupts these. Healthy, proliferating cells have much lower complex levels and are correspondingly less affected.

Q4: What is the difference vs other senolytics?¶

Most senolytics (dasatinib, quercetin) target BCL-2 family proteins broadly. FOXO4-DRI targets a specific protein-protein interaction unique to senescent cell biology — the FOXO4-p53 nuclear complex — potentially providing greater senescent cell selectivity.

Q5: What QC is unique to FOXO4-DRI?¶

Beyond standard tests: chiral amino acid analysis confirms all D-configuration residues; MALDI-TOF MS for accurate mass of this larger 47-amino acid peptide. All in batch-specific COA.

Key Research References¶

Reference	PMID	Key Finding
Baar MP et al. "Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging." Cell. 2017;169(1):132–147.e16.	28340339	FOXO4-DRI displaces FOXO4 from p53 in senescent cells, triggering p53-mediated apoptosis; restores fitness and hair density in naturally aged and progeroid mouse models
de Keizer PLJ. "The Fountain of Youth by Targeting Senescent Cells?" Trends Mol Med. 2017;23(1):6–17.	28041565	Review of senolytic strategies including FOXO4-DRI as a targeted protein-protein interaction disruptor for senescent cell clearance

Stability & Storage¶

Condition	Degradation Profile
D-Retro-Inverso Stability	All D-amino acids with reversed sequence — essentially invisible to proteases. Dramatically extended half-life compared to L-peptide counterparts
Lyophilized Storage	Standard peptide stability; 24 months at 2–8°C in desiccated environment, protect from light
Neutral pH (6.0–7.5)	Stable; excellent protease resistance across a range of pH conditions due to D-amino acid backbone
Reconstituted Solution	24 h at 2–8°C; aliquot and freeze at −20°C for extended use. Avoid repeated freeze-thaw
47-mer Handling	Larger peptide (MW ~4,316 Da) — use siliconized vials and low-retention tips to minimize non-specific adsorption

Source & Purchase¶

For research-grade FOXO4 DRI and related compounds in this category, visit the PeptideSourceHub category page for bulk pricing and available specifications.

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