| 名稱 | Picropodophyllin |
| 描述 | Picropodophyllin (Picropodophyllin (PPP)) (PPP) is a specific IGF-1R inhibitor (IC50: 1 nM). Picropodophyllin specifically inhibits the activity and downregulates the cellular expression of IGF1R without interfering with activities of other growth factor receptors, such as receptors for insulin, epidermal growth factor, platelet-derived growth factor, fibroblast growth factor and mast/stem cell growth factor (KIT). |
| 細(xì)胞實(shí)驗(yàn) | The determinations are performed using the Cell proliferation kit II, which is based on colorimetric change of the yellow tetrazolium salt 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt in orange formazan dye by the respiratory chain of viable cell. All of the standards and experiments are performed in triplicates. (Only for Reference) |
| 激酶實(shí)驗(yàn) | In vitro tyrosine kinase assays.: Assay of IGF-1R-catalyzed substrate phosphorylation of pTG, using a 96-well plate tyrosine kinase assay kit, is performed. We use recombinant epidermal growth factor receptor, immunoprecipitated IR from HEPG2, immunoprecipitated IGF-1R from P6 cells, and IGF-1R immunodepleted supernatant from P6 (representing "non-IGF-1R tyrosine kinases"). After 30-min treatment of the receptors with the desired compounds in the kinase buffer [50 mM HEPES buffer (pH 7.4), 20 mM MgCl2, 0.1 MnCl2, and 0.2 Na3VO4], the kinase reaction is activated by addition of ATP. The phosphorylated polymer substrate is probed with a phosphotyrosine-specific monoclonal antibody conjugated to horseradish peroxidase, clone PT-66. Color is developed with horseradish peroxidase chromogenic substrate O-phenylenediamine dihydrochloride and quantitated by spectrophotometry (ELISA reader). IGF-1R tyrosine autophosphorylation is analyzed by a sandwich ELISA assay. Briefly, 96-well plates are coated overnight at 4°C with 1 μg/well of an antibody to IGF-1R β-subunit. The plates are blocked with 1% BSA in PBS Tween for 1 h, and then 80 μg/well of total protein lysate from the P6 cell line is added. As a negative control we use total protein lysate from the R- cell line. The investigated compounds are added in tyrosine kinase buffer without ATP at room temperature for 30 min before kinase activation with ATP. Kinase assay is performed using the Sigma kit (see above). After spectrophotometry the IC50 values of inhibitors are determined using the REGRESSION function of Statistica program. |
| 體外活性 | 在完整細(xì)胞中，PPP有效抑制IGF-1激活的IGF-1R、Akt (Ser 473)和Erk1/2的磷酸化。Picropodophyllin特異性抑制細(xì)胞生長，并在培養(yǎng)的IGF-1R陽性腫瘤細(xì)胞中誘導(dǎo)凋亡。[1] Picropodophyllin與ABT-737和ABT-199協(xié)同作用，通過進(jìn)一步降低細(xì)胞活性和增強(qiáng)凋亡，從而增強(qiáng)對HMCL、原發(fā)性人MM細(xì)胞和小鼠5T33 mM細(xì)胞的敏感性。[3] Picropodophyllin和索拉非尼協(xié)同抑制肝細(xì)胞癌細(xì)胞的增殖和移動性。[4] |
| 體內(nèi)活性 | 在SCID小鼠中，通過人類ES-1、BE和PC3細(xì)胞外植后，Picropodophyllin（20 mg/kg/12 h，i.p.）能引起腫瘤完全消退。[1] 在5T33 mM小鼠模型中，Picropodophyllin同樣展現(xiàn)出顯著的抗腫瘤活性，并顯著延長生存期。[2] |
| 存儲條件 | Keep away from moisture
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (4.83 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 61.25 mg/mL (147.8 mM), Sonication is recommended.
Ethanol : 1 mg/mL (2.41 mM), Heating is recommended.
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| 關(guān)鍵字 | T3S0027 | Picropodophyllin (PPP) | Picropodophyllin | IGF-1R | IGF1R | AXL-1717 | AXL 1717 | Apoptosis |
| 相關(guān)產(chǎn)品 | Urea | Formamide | Dimethyl phthalate | Aceglutamide | Alginic acid | Dextran sulfate sodium salt (MW 5000) | Metronidazole | Sildenafil citrate | Citric Acid Triammonium | Stavudine | Tamoxifen | Adenosine |
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