1. Protein Tyrosine Kinase/RTK
  2. IGF-1R

AXL1717 (Synonyms: Picropodophyllotoxin; Picropodophyllin; PPP)

Cat. No.: HY-15494 Purity: 99.58%
Data Sheet SDS Handling Instructions

AXL1717 is a selective insulin-like growth factor-1 receptor (IGF-1R) inhibitor with IC50 of 1 nM.

For research use only. We do not sell to patients.
AXL1717 Chemical Structure

AXL1717 Chemical Structure

CAS No. : 477-47-4

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $77 In-stock
5 mg $70 In-stock
10 mg $90 In-stock
50 mg $360 In-stock
100 mg $610 In-stock
200 mg   Get quote  
500 mg   Get quote  

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    AXL1717 purchased from MCE. Usage Cited in: Acta Pharmacol Sin. 2016 Feb;37(2):217-27.

    The phosphorylation of IGF-1R is observed by a Western blot assay after the cells are pretreated with PPP 50 nM or a diluent for 60 min and deprived of insulin for 5 min.

    AXL1717 purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Kinobead western Blot readout for selected inhibitor:protein combinations.

    AXL1717 purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Immunoblot analysis in MV-4-11 cells and MOLM-13, FLT3-WT and FLT3-ITD transfected HEK293 cells, and Ba/F3 FLT3-ITD cells revealed FLT3 target engagement for Golvatinib and Cabozantinib.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    AXL1717 is a selective insulin-like growth factor-1 receptor (IGF-1R) inhibitor with IC50 of 1 nM.

    IC50 & Target

    IC50: 1 nM (IGF-1R)

    In Vitro

    In intact cells, AXL1717 efficiently inhibits IGF-1-stimulated IGF-1R, Akt (Ser 473) and Erk1/2 phosphorylation. AXL1717 specifically inhibits cell growth, and induces apoptosis in cultured IGF-1R-positive tumor cells[1]. AXL1717 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]. AXL1717 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, AXL1717 (20 mg/kg/12 h, i.p.) causes complete tumor regression[1]. In the 5T33MM mouse model, AXL1717 also shows a marked antitumor activity, and causes a significant increase in survival[2].

    Clinical Trial
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    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 2.4131 mL 12.0653 mL 24.1307 mL
    5 mM 0.4826 mL 2.4131 mL 4.8261 mL
    10 mM 0.2413 mL 1.2065 mL 2.4131 mL
    Please refer to the solubility information to select the appropriate solvent.
    Kinase Assay
    [1]

    Assay of IGF-1R-catalyzed substrate phosphorylation of pTG, using a 96-well plate tyrosine kinase assay kit, is performed. Recombinant epidermal growth factor receptor, immunoprecipitated IR from HEPG2, immunoprecipitated IGF-1R from P6 cells, and IGF-1R immunodepleted supernatant from P6 are used. 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. The investigated compounds are added in tyrosine kinase buffer without ATP at room temperature for 30 min before kinase activation with ATP. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    AXL1717 is formulated in DMSO: vegetable oil, 10:1 (v/v).

    Four to 5-week-old pathogen-free SCID mice are used and housed within plastic isolators in a sterile facility. ES-1, BE, and PC3 cells (all proved to express IGF-1R), or R-v-src (IGF-1R negative) and P12 (overexpressing IGF-1 and IGF-1R), are injected s.c. at 107 cells/mice in a 0.2 mL volume of sterile saline solution. Immunocompetent Balb-c mice are injected with 107JC murine breast cancer cells per mouse in 0.15 mL volume of sterile saline solution. Experimental treatments with AXL1717 (20 mg/kg/12 h) are performed by daily i.p. injections of the compound in 10 μL volume of DMSO: vegetable oil, 10:1 (v/v). Control mice are treated with the vehicle only. Three animals are treated in each group. Tumor growth is measured every second day using vernier calipers, and the tumor volumes are calculated as a product of length × width × height. The mice are carefully observed for the presence of side effects and are sacrificed at the end of the experiments for histological analysis of the lesions. A separate experiment on AXL1717-treated (systemically and locally) tumor-free mice, including histological analyses of various organs, confirms previous observations that AXL1717 appears to be nontoxic. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    414.41

    Formula

    C₂₂H₂₂O₈

    CAS No.

    477-47-4

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    10 mM in DMSO

    AXL1717 (PPP) is prepared in vehicle (0.1 mol/L sodium citrate buffer, pH 4.0)[6].

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    References

    Purity: 99.58%

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    Cat. No.:
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