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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
FOXO4-DRI (Forkhead box O4 - D-retro inverso) specifically binds to and competitively disrupts the interaction between the transcription factor FOXO4 and the tumor suppressor p53, thereby interfering with senescence‑associated survival pathways.
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| ln Vitro |
In senescent TM3 Leydig cells, FOXO4-DRI (25 mM; 3 days) induces apoptosis and causes nuclear exclusion of active p53 [1]. The senescence level of PDL9 cells is significantly reduced by FOXO4-DRI (25 μM; 5 days) [2].
In vitro, FOXO4‑DRI induces p53‑mediated apoptosis in senescent cells without affecting healthy cell viability. It has been demonstrated to alleviate age‑related testosterone secretion insufficiency by specifically targeting senescent Leydig cells in aged mice. |
| ln Vivo |
In naturally aging rats, FOXO4-DRI (5 mg/kg; ip; every other day for three administrations) enhances the testicular microenvironment and relieves inadequate testosterone secretion [1].
In animal studies, systemic administration of FOXO4‑DRI selectively eliminates p16Ink4a‑positive senescent cells in aged mice, restoring fur density, renal function, and physical performance, and contributing to improvement in biological age of young tissues. |
| Enzyme Assay |
Non‑cellular inhibition of the FOXO4‑p53 interaction is assessed using purified proteins in a fluorescence polarization (FP) or ELISA‑based binding assay. Increasing concentrations of FOXO4‑DRI are incubated with recombinant FOXO4 and p53 to determine the peptide's ability to disrupt complex formation, with IC50 values derived from competition binding curves.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: Senescent Leydig cells Tested Concentrations: 25 mM Incubation Duration: 3 days Experimental Results: decreased the viability of senescent as compared to normal TM3 Leydig cells. Apoptosis Analysis[1] Cell Types: Senescent Leydig cells Tested Concentrations: 25 mM Incubation Duration: 3 days Experimental Results: The apoptosis rate increased from 10% to 27%. Western Blot Analysis[2] Cell Types: PDL9 cells Tested Concentrations: 25 μM Incubation Duration: 5 days Experimental Results: diminished the protein levels of representative senescent markers, including p16, p21, and p53. RT-PCR[2] Cell Types: PDL9 cells Tested Concentrations: 25 μM Incubation Duration: 5 days Experimental Results: Enhanced SOX9 expression, and decreased MMP12 and MMP13 expression. For cell‑based studies, senescent human primary fibroblasts or other senescence‑positive cell lines are treated with FOXO4‑DRI (1‑50 uM) for 24-72 h. Apoptosis is quantified using Annexin V/PI staining, caspase‑3/7 activation assays, and measurement of p53 transcriptional activity by qRT‑PCR or reporter gene analysis. |
| Animal Protocol |
Animal/Disease Models: Naturally aged male C57BL/6 mice (20-24 months old)[1]
Doses: 5 mg/kg Route of Administration: intraperitoneal (ip)injection, every other day for three administrations Experimental Results: Increased serum testosterone levels. Increased levels of both 3β-HSD and CYP11A1. diminished interstitial SA-β-gal activity and lowered levels of senescence-associated proteins p53, p21, and p16. diminished the levels of IL- 1β, IL-6 and TGF-β. In aged murine models, FOXO4‑DRI is administered intraperitoneally or subcutaneously (2-10 mg/kg) every other day for 2-4 weeks. Senolytic efficacy is evaluated by immunostaining for p16Ink4a and senescence‑associated beta‑galactosidase in kidney, muscle, and adipose tissue, alongside functional tests for physical activity and metabolic parameters. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for FOXO4‑DRI are limited, as the peptide is primarily used as a research tool. Peptide‑based agents of similar molecular weight typically exhibit rapid clearance from circulation with short half‑lives (minutes to a few hours) and require parenteral administration to bypass gastrointestinal degradation.
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| Toxicity/Toxicokinetics |
Acute toxicity studies have not been systematically reported for FOXO4‑DRI. However, based on its mechanism as a p53‑mediated senolytic agent, potential on‑target risks include transient depletion of p53‑dependent physiological senescence, which may affect tissue repair and regeneration. No significant off‑target cytotoxicity has been observed in standard preclinical safety assessments.
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| References |
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| Additional Infomation |
FOXO4‑DRI is strictly a research‑grade peptide not yet approved for human therapy. Its senolytic activity has generated strong interest in the fields of aging biology and therapeutic elimination of senescent cells in age‑related disorders. Ongoing preclinical research is exploring its utility in neurodegenerative diseases, osteoarthritis, and metabolic dysfunction. No clinical trials have been registered to date.
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| Molecular Formula |
C228H388N86O64
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|---|---|
| Molecular Weight |
5358.06
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| Exact Mass |
4520.814
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| CAS # |
2460055-10-9
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| Related CAS # |
FOXO4-DRI acetate
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| PubChem CID |
167312269
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
92
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| Rotatable Bond Count |
194
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| Heavy Atom Count |
378
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| Complexity |
13500
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| Defined Atom Stereocenter Count |
45
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| SMILES |
CC[C@@H](C)[C@H](C(=O)N[C@H](C)C(=O)N[C@H](CCC(=O)N)C(=O)N[C@H](CO)C(=O)N[C@H]([C@H](C)CC)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCC(=O)O)C(=O)N[C@H](C)C(=O)N[C@H](CC1=CC=C(C=C1)O)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(=O)N)C(=O)N[C@H](CC(=O)N)C(=O)NCC(=O)N[C@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@H](C)C(=O)N[C@H](CC(=O)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CO)C(=O)NCC(=O)NCC(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCNC(=N)N)C(=O)N4CCC[C@@H]4C(=O)N5CCC[C@@H]5C(=O)N6CCC[C@@H]6C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCC(=O)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCNC(=N)N)C(=O)NCC(=O)O)NC(=O)[C@@H](CCC(=O)O)NC(=O)[C@@H](CO)NC(=O)[C@@H](C)NC(=O)[C@H]7CCCN7C(=O)[C@@H](CCC(=O)O)NC(=O)[C@@H](CCCCN)NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H]([C@H](C)O)NC(=O)[C@@H](CC(C)C)N
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| InChi Key |
PFXXSSUGMGVDLB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H32Cl2N4O2.C30H33ClN4O2.C30H34N4O3.C30H34N4O2.C28H34Cl2N4O2.C26H31BrFN5O2.C26H30BrFN4O2.C26H30Cl2N4O2.C22H20N4O/c32-27-14-16-30(33)35-29(27)21-25(22-34)31(38)36-28(15-9-23-7-3-1-4-8-23)24-10-12-26(13-11-24)39-20-19-37-17-5-2-6-18-37;1-2-7-28(22-11-14-26(15-12-22)37-19-18-35-16-4-3-5-17-35)34-30(36)24(21-32)20-25-13-10-23-8-6-9-27(31)29(23)33-25;1-2-7-27(22-11-14-26(15-12-22)37-19-18-34-16-4-3-5-17-34)33-30(36)24(21-31)20-25-13-10-23-8-6-9-28(35)29(23)32-25;1-2-8-28(24-12-15-27(16-13-24)36-20-19-34-17-6-3-7-18-34)33-30(35)25(22-31)21-26-14-11-23-9-4-5-10-29(23)32-26;1-20(2)6-12-25(33-28(35)22(19-31)18-26-24(29)11-13-27(30)32-26)21-7-9-23(10-8-21)36-17-16-34-14-4-3-5-15-34;1-3-4-23(31-26(34)20(18-29)17-24-22(28)9-10-25(27)30-24)19-5-7-21(8-6-19)35-16-15-33-13-11-32(2)12-14-33;1-2-6-23(31-26(33)20(18-29)17-24-22(28)11-12-25(27)30-24)19-7-9-21(10-8-19)34-16-15-32-13-4-3-5-14-32;1-2-6-23(31-26(33)20(18-29)17-24-22(27)11-12-25(28)30-24)19-7-9-21(10-8-19)34-16-15-32-13-4-3-5-14-32;1-2-7-20(16-8-4-3-5-9-16)26-22(27)18(15-23)14-19-12-11-17-10-6-13-24-21(17)25-19/h1,3-4,7-8,10-14,16,21,28H,2,5-6,9,15,17-20H2,(H,36,38);6,8-15,20,28H,2-5,7,16-19H2,1H3,(H,34,36);6,8-15,20,27,35H,2-5,7,16-19H2,1H3,(H,33,36);4-5,9-16,21,28H,2-3,6-8,17-20H2,1H3,(H,33,35);7-11,13,18,20,25H,3-6,12,14-17H2,1-2H3,(H,33,35);5-10,17,23H,3-4,11-16H2,1-2H3,(H,31,34);2*7-12,17,23H,2-6,13-16H2,1H3,(H,31,33);3-6,8-14,20H,2,7H2,1H3,(H,26,27)
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| Chemical Name |
3-(6-bromo-3-fluoropyridin-2-yl)-2-cyano-N-[1-[4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]butyl]prop-2-enamide;3-(6-bromo-3-fluoropyridin-2-yl)-2-cyano-N-[1-[4-(2-piperidin-1-ylethoxy)phenyl]butyl]prop-2-enamide;3-(8-chloroquinolin-2-yl)-2-cyano-N-[1-[4-(2-piperidin-1-ylethoxy)phenyl]butyl]prop-2-enamide;2-cyano-3-(3,6-dichloropyridin-2-yl)-N-[4-methyl-1-[4-(2-piperidin-1-ylethoxy)phenyl]pentyl]prop-2-enamide;2-cyano-3-(3,6-dichloropyridin-2-yl)-N-[3-phenyl-1-[4-(2-piperidin-1-ylethoxy)phenyl]propyl]prop-2-enamide;2-cyano-3-(3,6-dichloropyridin-2-yl)-N-[1-[4-(2-piperidin-1-ylethoxy)phenyl]butyl]prop-2-enamide;2-cyano-3-(8-hydroxyquinolin-2-yl)-N-[1-[4-(2-piperidin-1-ylethoxy)phenyl]butyl]prop-2-enamide;2-cyano-3-(1,8-naphthyridin-2-yl)-N-(1-phenylbutyl)prop-2-enamide;2-cyano-N-[1-[4-(2-piperidin-1-ylethoxy)phenyl]butyl]-3-quinolin-2-ylprop-2-enamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 50 mg/mL (9.33 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.1866 mL | 0.9332 mL | 1.8663 mL | |
| 5 mM | 0.0373 mL | 0.1866 mL | 0.3733 mL | |
| 10 mM | 0.0187 mL | 0.0933 mL | 0.1866 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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