| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| Other Sizes |
| Targets |
FOXO4-DRI acetate targets the FOXO4-p53 protein-protein interaction. It specifically binds to the p53 transactivation domain, disrupting the complex formed between FOXO4 and p53. This interaction is essential for the survival of senescent cells, and its disruption leads to p53-mediated apoptosis. The peptide's selectivity for senescent cells is a key feature of its mechanism.
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| ln Vitro |
In senescent TM3 Leydig cells, FOXO4-DRI (25 mM; 3 days) acetate promotes apoptosis and causes nuclear exclusion of active p53 [1]. The senescence level of PDL9 cells is greatly reduced by FOXO4-DRI (25 μM; 5 days) acetate [2].
In vitro, FOXO4-DRI acetate selectively induces apoptosis in senescent cells by disrupting FOXO4-p53 binding. It has been shown to reduce markers of senescence and promote the clearance of senescent cells in culture. It has also been demonstrated to induce apoptosis in keloid senescent fibroblasts. |
| ln Vivo |
In naturally aged rats, FOXO4-DRI (5 mg/kg; ip; every other day for three administrations) acetate enhances the testicular microenvironment and alleviates inadequate testosterone secretion [1].
In vivo, FOXO4-DRI acetate (5 mg/kg; i.p.; every other day for three administrations) alleviates testosterone secretion insufficiency and improves the testicular microenvironment in naturally aged mice. It has been shown to clear senescent cells and improve age-related phenotypes in mouse models. It reduces senescence markers, improves physical function, and extends healthspan in aged mice. |
| Enzyme Assay |
Non-cellular assays for FOXO4-DRI acetate involve measuring its ability to disrupt FOXO4-p53 binding using biophysical techniques such as surface plasmon resonance (SPR) or fluorescence polarization. The peptide is incubated with recombinant FOXO4 and p53 proteins, and the disruption of the complex is quantified.
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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. In vitro cellular assays: FOXO4-DRI acetate is tested on senescent cells in culture. Apoptosis induction is measured by caspase activation and Annexin V staining. Senescence markers (e.g., SA-β-gal) are assessed to confirm senolytic activity. |
| 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 vivo animal experiments: FOXO4-DRI acetate is administered to aged mice or mouse models of age-related diseases. Endpoints include clearance of senescent cells, reduction of senescence markers, improvement in physical function, and extension of healthspan. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties: FOXO4-DRI acetate is a cell-penetrating peptide. Its PK would be influenced by proteolytic degradation and clearance. It is typically administered via injection for in vivo studies.
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| Toxicity/Toxicokinetics |
Toxicological data for FOXO4-DRI acetate are limited. As a senolytic peptide, its safety profile has been evaluated in preclinical studies.
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| References |
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| Additional Infomation |
FOXO4-DRI acetate is a cell-penetrating peptide with senolytic activity. It is used in aging research to study the role of senescent cells in age-related diseases. It is not approved for clinical use.
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| Molecular Formula |
C228H388N86O64.0.145C2H4O2
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|---|---|
| Molecular Weight |
5366.77
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| Exact Mass |
948.445
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| Related CAS # |
FOXO4-DRI;2460055-10-9
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| PubChem CID |
72233564
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
15
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| Rotatable Bond Count |
32
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| Heavy Atom Count |
65
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| Complexity |
1640
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| Defined Atom Stereocenter Count |
6
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| SMILES |
CC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N.CC(=O)O
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| InChi Key |
KUOYHRQPSCEGDA-PXILYFGCSA-N
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| InChi Code |
InChI=1S/C34H60N14O12S.C2H4O2/c1-17(49)43-20(8-11-25(51)52)29(57)47-22(9-12-26(53)54)31(59)48-23(13-16-61-2)32(60)46-21(7-10-24(35)50)30(58)45-19(6-4-15-42-34(39)40)28(56)44-18(27(36)55)5-3-14-41-33(37)38;1-2(3)4/h18-23H,3-16H2,1-2H3,(H2,35,50)(H2,36,55)(H,43,49)(H,44,56)(H,45,58)(H,46,60)(H,47,57)(H,48,59)(H,51,52)(H,53,54)(H4,37,38,41)(H4,39,40,42);1H3,(H,3,4)/t18-,19-,20-,21-,22-,23-;/m0./s1
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| Chemical Name |
(4S)-4-acetamido-5-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid;acetic acid
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 0.1863 mL | 0.9317 mL | 1.8633 mL | |
| 5 mM | 0.0373 mL | 0.1863 mL | 0.3727 mL | |
| 10 mM | 0.0186 mL | 0.0932 mL | 0.1863 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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