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受注：045-509-1970 |
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化学情報
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C30H30Cl2N4O4 |
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| 分子量 | 581.5 | CAS No. | 890090-75-2 | |
| Solubility (25°C)* | 体外 | DMSO | 100 mg/mL (171.96 mM) | |
| Ethanol | 100 mg/mL (171.96 mM) | |||
| Water | Insoluble | |||
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Nutlin-3 is a potent and selective Mdm2 (RING finger-dependent ubiquitin protein ligase for itself and p53) antagonist with IC50 of 90 nM in a cell-free assay; stabilizes p73 in p53-deficient cells. |
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| in vitro | Nutlin-3 potently inhibits the MDM2-p53 interaction, leading to the activation of the p53 pathway. Nutlin-3 treatment induces the expression of MDM2 and p21, and displays potent antiproliferative activity with IC50 of ~1.5 μM, only in cells with wild-type p53 such as HCT116, RKO and SJSA-1, but not in the mutant p53 cell lines SW480 and MDA-MB-435. In SJSA-1 cells, Nutlin-3 treatment at 10 μM for 48 hours significantly induces caspase-dependent cell apoptosis by ~45%. Although Nutlin-3 also inhibits the growth and viability of human skin (1043SK) and mouse embryo (NIH/3T3) with IC50 of 2.2 μM and 1.3 μM, respectively, cells remain viable 1 week post-treatment even at 10 μM of Nutlin-3, in contrast with the SJSA-1 cells with viability lost at 3 μM of Nutlin-3 treatment. [1] Nutlin-3 does not induce the phosphorylation of p53 on key serine residues and reveals no difference in their sequence-specific DNA binding and ability to transactivate p53 target genes compared with phosphorylated p53 induced by the genotoxic drugs doxorubicin and etoposide, demonstrating that phosphorylation of p53 on key serines is dispensable for transcriptional activation and apoptosis. [2] Although binding less efficiently to MDMX than to MDM2, Nutlin-3 can block the MDMX–p53 interaction and induce the p53 pathway in retinoblastoma cells (Weri1) with IC50 of 0.7 μM. [3] Nutlin-3 at 30 μM also disrupts endogenous p73-HDM2 interaction and enhances the stability and proapoptotic activities of p73, leading to the dose-dependent cell growth inhibition and apoptosis induction in cells without wild-type p53. [4] |
| in vivo | Oral administration of Nutlin-3 at 200 mg/kg twice daily for 3 weeks significantly inhibits the tumor growth of SJAS-1 xenografts by 90%, comparable with the effect of doxorubicin treatment with 81% inhibition of tumor growth. [1] |
プロトコル(参考用のみ)
| キナーゼアッセイ | Biacore study | |
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| Competition assay is performed on a Biacore S51. A Series S Sensor chip CM5 is utilized for the immobilization of a PentaHis antibody for capture of the His-tagged p53. The level of capture is ~200 response units (1 response unit corresponds to 1 pg of protein per mm2). The concentration of MDM2 protein is kept constant at 300 nM. Nutlin-3 is dissolved in DMSO at 10 mM and further diluted to make a concentration series of Nutlin-3 in each MDM2 test sample. The assay is run at 25 °C in running buffer (10 mM Hepes, 0.15 M NaCl, 2% DMSO). MDM2-p53 binding in the presence of Nutlin-3 is calculated as a percentage of binding in the absence of Nutlin-3 and IC50 is calculate | ||
| 細胞アッセイ | 細胞株 | HCT116, RKO, SJSA-1, SW480, and MDA-MB-435 |
| 濃度 | Dissolved in DMSO, final concentrations ~ 30 μM | |
| 反応時間 | 8, 24, and 48 hours | |
| 実験の流れ | Cells are exposed to various concentrations of Nutlin-3 for 8, 24 and 48 hours. The transcriptional levels of p21 and MDM2 genes are analyzed by real-time PCR, and protein levels by western blotting. Cell viability is measured by the MTT assay. Cell apoptosis is determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining with flow cytometry and fluorescence microscopy. |
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| 動物実験 | 動物モデル | Athymic female nude mice (Nu/Nu-nuBR) injected subcutaneously with SJSA-1 cells |
| 投薬量 | 200 mg/kg | |
| 投与方法 | Orally, twice a day | |
参考
カスタマーフィードバック
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Data from [Data independently produced by Int J Oncol, 2014, 44, 761-8]
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Data from [Cell Death Dis, 2012, 3, e294]
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Data from [Cell Death Dis, 2011, 2, e243]
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| High-throughput evaluation of genetic variants with prime editing sensor libraries [ Nat Biotechnol, 2024, 10.1038/s41587-024-02172-9] | PubMed: 38472508 |
| A homoeostatic switch causing glycerol-3-phosphate and phosphoethanolamine accumulation triggers senescence by rewiring lipid metabolism [ Nat Metab, 2024, 6(2):323-342] | PubMed: 38409325 |
| Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity [ Cancer Discov, 2023, 13(2):432-453] | PubMed: 36302222 |
| Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity [ Cancer Discov, 2023, 13(2):432-453] | PubMed: 36302222 |
| Comprehensive analysis of pyroptosis-related gene signatures for glioblastoma immune microenvironment and target therapy [ Cell Prolif, 2023, e13376.] | PubMed: 36681858 |
| Tumor suppressor p53 mediates interleukin-6 expression to enable cancer cell evasion of genotoxic stress [ Cell Death Discov, 2023, 9(1):340] | PubMed: 37696858 |
| Tumor suppressor p53 mediates interleukin-6 expression to enable cancer cell evasion of genotoxic stress [ Cell Death Discov, 2023, 9(1):340] | PubMed: 37696858 |
| Carnitine o-octanoyltransferase is a p53 target that promotes oxidative metabolism and cell survival following nutrient starvation [ J Biol Chem, 2023, 299(7):104908] | PubMed: 37307919 |
| Carnitine o-octanoyltransferase is a p53 target that promotes oxidative metabolism and cell survival following nutrient starvation [ J Biol Chem, 2023, 299(7):104908] | PubMed: 37307919 |
| p53 controls choice between apoptotic and non-apoptotic death following DNA damage [ bioRxiv, 2023, 2023.01.17.524444] | PubMed: 36712034 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。