peptide wiki

FOXO4-DRI

aka FOXO4-D-Retro-Inverso

Nootropic / Cognitive

Mechanism

FOXO4-DRI is a D-retro-inverso peptide designed to disrupt the FOXO4-p53 interaction in senescent cells. It is studied as a senolytic agent that selectively induces apoptosis in senescent cells while sparing normal cells.

Identification

CAS number2460055-10-9
Molecular formulaC228H388N86O64
SequenceLTLRKEPASEIAQSILEAYSQNGWANRRSGGKRPPPRRRQRRKKRG
Typical dose1 mg subcutaneous, repeated on alternating days (e.g. days 1, 3, 5) per cycle; original mouse research used 5 mg/kg × 3 doses
Half-life~2–6 hours (estimated preclinical; no human PK data available)

Vendors selling FOXO4-DRI

VendorSizePriceListed purityTrust
Glacier Aminos 10 mg $134.99 99
BioLongevity Labs 10 mg $274.97 96
Orbitrex Peptides 10 mg $189.99 95
Ion Peptide 10 mg $119.00 95
Peptide Tech 10 mg $148.99 94
Skye Peptides 15 mg $169.00 90
Qihang Peptide 87
Verified Peptides 10 mg $220.00 86
Simple Peptide $180.00 85
Peptidegurus 10 mg 84
Cocer Peptides 10 mg $500.00 82
OROS Research 10 mg 79
MEI-PEPETIDE 10 mg $221.00 48
MJT peptides 10 mg $375.00 39
Apollo Peptide Sciences 10 mg
AMC Essentials 10 mg $99.99
Alpha Omega 10 mg $180.00
Atomik Labz 14 mg $199.00
Biotech Peptides 10 mg $270.00
Core Peptides 10 mg $235.00
Kimera Chems $151.99
Oasis Labs 10 mg $217.50
Paramount Peptides 15 mg $300.00
Peptide Crafters 12 mg $165.00
Polaris Peptides 10 mg $250.00
Solution Peptides 14 mg $199.00

Research

Targeting the FOXO4-p53 axis by retro-inverso peptide senolytic agents: a pharmacological strategy to mitigate brain aging and cognitive decline
Alameen AAM, Al-Kuraishy HM, Fawzy MN, Batiha GE. · Naunyn-Schmiedeberg's archives of pharmacology (2026) · review

Cellular senescence, driven by the interaction between FOXO4 and p53, is increasingly recognized as a crucial mechanism in brain aging and the development of neurodegenerative disorders.

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Acylglycerol Kinase Sensitizes Glioblastoma to Temozolomide via Limiting Mitochondrial Damage Related Cellular Senescence
Ning N, Wang C, Gao T, Ma J, Ding M, Zhang F, Liu Q, Zhang W, Gong L. · Molecular carcinogenesis (2026) ·

Temozolomide (TMZ) is still the first-line drug for glioblastoma (GBM) treatment though tumor cell resistance remains a major challenge.

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The right time, the right cell: the potential for precision senotherapy in pulmonary arterial hypertension
Hirsch K, Horn AG, Donato AJ, Schulze KM. · American journal of physiology. Lung cellular and molecular physiology (2026) · review

Pulmonary arterial hypertension (PAH) is a fatal vasculopathy driven by proinflammatory signaling that leads to pulmonary vascular remodeling and ultimately, right ventricular failure. Existing therapies fail to eliminate dysfunctional cells or reverse pathologic remodeling.

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FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway
Hu Z, Li F, Hu C, Shan Q, Tang Z, Jiang M, Yi X, Chen X, Jin L, Wang X, Wang Y. · Frontiers in bioengineering and biotechnology (2025) · animal

Objectives Endothelial cell dysfunction during aging is a key driver of vascular aging and related diseases; however, effective strategies to selectively eliminate senescent endothelial cells and restore vascular function remain lacking.

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The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI
Bourgeois B, Spreitzer E, Platero-Rochart D, Paar M, Zhou Q, Usluer S, de Keizer PLJ, Burgering BMT, Sánchez-Murcia PA, Madl T. · Nature communications (2025) ·

A central process contributing to the phenotype of aging is cellular senescence. We recently identified the FOXO4 - p53 axis as pivotal in maintaining the viability of senescent cells, and that senescent cells can be targeted selectively with the senolytic peptide FOXO4-DRI.

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FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation
Kong YX, Li ZS, Liu YB, Pan B, Fu X, Xiao R, Yan L. · Communications biology (2025) ·

Keloids are pathological scars exhibiting tumour-like aggressiveness and high recurrence rate.

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Senotherapeutics for Brain Aging Management
Saliev T, Singh PB. · Neurology international (2025) · review

Brain aging is a progressive process marked by cellular dysfunction, chronic inflammation, and increased susceptibility to neurodegenerative diseases.

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Advantages and Possibility of Transcription Factors FOXOs in HCC
Xiufeng G, Zhiping H, Jingzhi W. · Cell biochemistry and function (2025) · review

The forkhead frame O protein (forkhead box class O proteins, FOXOs) is a highly conserved family of transcription factors, consisting of four members: FOXO 1, FOXO 3, FOXO 4, and FOXO 6.

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The Role of Senolytics in Osteoporosis
Chen E, Zhang J, Chen H, Li W. · Biomolecules (2025) · review

Cellular senescence is a fundamental contributor to numerous dysfunctions and degenerative diseases, including osteoporosis. In genetically modified and preclinical animal models, therapeutic strategies targeting persistent senescent cells have been shown to delay and prevent osteoporosis.

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FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells
Li Y, Zhang C, Cheng H, Lv L, Zhu X, Ma M, Xu Z, He J, Xie Y, Yang X, Liang X, Deng C, Liu G. · Experimental gerontology (2024) · animal

Male ageing is always accompanied by decreased fertility. The forkhead O (FOXO) transcription factor FOXO4 is reported to be highly expressed in senescent cells. Upon activation, it binds p53 in the nucleus, preventing senescent cell apoptosis and maintaining senescent cells in situ.

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Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From <i>in vitro</i> Expanded Human Chondrocytes
Huang Y, He Y, Makarcyzk MJ, Lin H. · Frontiers in bioengineering and biotechnology (2021) · in-vitro

Autologous chondrocyte implantation (ACI) is a procedure used to treat articular cartilage injuries and prevent the onset of post-traumatic osteoarthritis.

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FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice
Zhang C, Xie Y, Chen H, Lv L, Yao J, Zhang M, Xia K, Feng X, Li Y, Liang X, Sun X, Deng C, Liu G. · Aging (2020) · animal

Male late-onset hypogonadism is an age-related disease, the core mechanism of which is dysfunction of senescent Leydig cells. Recent studies have shown that elimination of senescent cells can restore proper homeostasis to aging tissue.

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