Picropodophyllin (PPP)

製品コードS7668 バッチS766802

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 (warmed with 50ºC water bath) 82 mg/mL (197.87 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
8%DMSO 92%Corn oil

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 3.000mg/ml (7.24mM) Taking the 1 mL working solution as an example, add 80 μL of 37.5 mg/ml clear DMSO stock solution to 920 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <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, Picropodophyllin (PPP) efficiently inhibits IGF-1-stimulated IGF-1R, Akt (Ser 473) and Erk1/2 phosphorylation. It specifically inhibits cell growth, and induces apoptosis in cultured IGF-1R-positive tumor cells. [1] This compound 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] It also synergistically suppresses the proliferation and motility of hepatocellular carcinoma cells. [4]
in vivo

In SCID mice xenografted with human ES-1, BE, and PC3, Picropodophyllin (PPP) (20 mg/kg/12 h, i.p.) causes complete tumor regression. [1] In the 5T33MM mouse model, it 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 Picropodophyllin (PPP) 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. This compound is 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

All of the standards and experiments for Picropodophyllin (PPP) are performed in triplicates 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.
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.

参考

  • https://pubmed.ncbi.nlm.nih.gov/14729630/
  • https://pubmed.ncbi.nlm.nih.gov/16046527/
  • https://pubmed.ncbi.nlm.nih.gov/25008202/
  • https://pubmed.ncbi.nlm.nih.gov/25289088/

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：

Disrupting AGR2/IGF1 paracrine and reciprocal signaling for pancreatic cancer therapy [ Cell Rep Med, 2025, 6(2):101927] PubMed: 39914384
Viral insulin/IGF-like peptides inhibit IGF-1 receptor signaling to enhance viral replication [ Cell Rep, 2025, 44(8):116149] PubMed: 40829596
Picropodophyllin, an IGF‑1 receptor inhibitor, enhances oxaliplatin efficacy in chemoresistant colorectal cancer HCT116 cells by reducing metastatic potential [ Oncol Lett, 2025, 29(5):220] PubMed: 40103601
Nutrient-regulated dynamics of chondroprogenitors in the postnatal murine growth plate [ Bone Res, 2023, 11(1):20] PubMed: 37080994
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
Scalable generation of sensory neurons from human pluripotent stem cells [ Stem Cell Reports, 2023, 18(4):1030-1047] PubMed: 37044067
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

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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