Picropodophyllin (PPP)

製品コードS7668 バッチS766801

印刷

化学情報

Chemical Structure Synonyms AXL1717 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C22H22O8
分子量 414.41 CAS No. 477-47-4
Solubility (25°C)* 体外 DMSO 82 mg/mL warmed with 50ºC water bath (197.87 mM)
Ethanol 1 mg/mL warmed with 50ºC water bath (2.41 mM)
Water Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Picropodophyllin (PPP, AXL1717) is a IGF-1R inhibitor with IC50 of 1 nM. It displays selectivity for IGF-1R and does not coinhibit tyrosine phosphorylation the IR, or of a selected panel of receptors less related to IGF-IR(FGF-R, PDGF-R, OR EGF-R). Picropodophyllin (PPP) induces apoptosis with antineoplastic activity.
in vitro In intact cells, PPP efficiently inhibits IGF-1-stimulated IGF-1R, Akt (Ser 473) and Erk1/2 phosphorylation. Picropodophyllin specifically inhibits cell growth, and induces apoptosis in cultured IGF-1R-positive tumor cells. [1] Picropodophyllin synergistically sensitizes HMCL, primary human MM and murine 5T33MM cells to ABT-737 and ABT-199 by further decreasing cell viability and enhancing apoptosis. [3] Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells. [4]
in vivo In SCID mice xenografted with human ES-1, BE, and PC3, Picropodophyllin (20 mg/kg/12 h, i.p.) causes complete tumor regression. [1] In the 5T33MM mouse model, Picropodophyllin also shows a marked antitumor activity, and causes a significant increase in survival. [2]

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 Melanoma cells (FM 55, SK-MEL-28, SK-MEL-5, C8161, DFB, DFW and AA), sarcoma cells (RD-ES), breast carcinoma cells (MCF 7), prostate carcinoma cells (PC3), hepatoma cells (HepG2) and embryonic mouse fibroblasts (P6 and R-)
濃度 ~15 μM
反応時間 48 hours
実験の流れ

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.
動物実験 動物モデル SCID mice bearing ES-1, BE, or PC3 xenografts that express IGF-1R, or R- v-src (IGF-1R negative) and P12 (overexpressing IGF-1 and IGF-1R)
投薬量 20 mg/kg/12 h
投与方法 i.p.

カスタマーフィードバック

Data from [Data independently produced by , , Blood, 2013, 122(9):1621-33]

Data from [Data independently produced by , , Stem Cells, 2016, 34(4):820-31.]

Data from [Data independently produced by , , Cancer Sci, 2018, 109(4):1166-1176]

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：

Nutrient-regulated dynamics of chondroprogenitors in the postnatal murine growth plate [ Bone Res, 2023, 11(1):20] PubMed: 37080994
Synergy of 5-aminolevulinate supplement and CX3CR1 suppression promotes liver regeneration via elevated IGF-1 signaling [ Cell Rep, 2023, 42(8):112984] PubMed: 37578861
IGF1R Inhibition Enhances the Therapeutic Effects of Gq/11 Inhibition in Metastatic Uveal Melanoma Progression [ Mol Cancer Ther, 2023, 22(1):63-74] PubMed: 36223548
Inhibition of the epigenetically activated miR-483-5p/IGF-2 pathway results in rapid loss of meningioma tumor cell viability [ J Neurooncol, 2023, 162(1):109-118.] PubMed: 36809604
Effect of insulin-like growth factor system on luteinising angiogenesis [ Reprod Fertil, 2023, 4(2)e220057 RAF-22-0057] PubMed: 37052337
A Role for Insulin-like Growth Factor 1 in the Generation of Epileptic Spasms [ Ann Neurol, 2022, 10.1002/ana.26383] PubMed: 35467038
Hedgehog-responsive PDGFRa(+) fibroblasts maintain a unique pool of alveolar epithelial progenitor cells during alveologenesis [ Cell Rep, 2022, 39(1):110608] PubMed: 35385750
Coal dust nanoparticles induced pulmonary fibrosis by promoting inflammation and epithelial-mesenchymal transition via the NF-κB/NLRP3 pathway driven by IGF1/ROS-mediated AKT/GSK3β signals [ Cell Death Discov, 2022, 8(1):500] PubMed: 36581638
Cytochrome P450 27C1 Level Dictates Lung Cancer Tumorigenicity and Sensitivity towards Multiple Anticancer Agents and Its Potential Interplay with the IGF-1R/Akt/p53 Signaling Pathway [ Int J Mol Sci, 2022, 23(14)7853] PubMed: 35887201
Insulin-like growth factor 1 regulates excitatory synaptic transmission in pyramidal neurons from adult prefrontal cortex [ Neuropharmacology, 2022, 217:109204] PubMed: 35931212

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。

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