My cart
In the shopping cart is not goods, to choose and buy!
  • Product Name
  • Size
  • Quantity
  • Amount
    Selected items : 0 pieces Total : CHECK OUT()
    Torkinib (PP242)
    Torkinib (PP242)

    Price:
    Market Price:

    This product is for research use only, not for human use. We do not sell to patients.
    Number: - + Pieces(InventoryPieces)
    InvivoChem Cat #: V0176
    CAS #: 1092351-67-1Purity ≥98%

    Description: Torkinib (also known as PP242) is a novel, potent and selective ATP-competitive mTOR (mammalian target of rapamycin) inhibitor with potential anticancer activity. It inhibits mTOR with IC50 of 8 nM in cell-free assays; it targets both mTOR complexes (mTORC) with >10- and 100-fold selectivity for mTOR than PI3Kδ or PI3Kα/β/γ, respectively. Torkinib suppresses bladder cancer cell proliferation and migration through deactivating the mammalian target of rapamycin complex 2/AKT1 signaling pathway. PP242 shows strong antitumor activity in a pheochromocytoma PC12 cell tumor model. PP242 suppresses cell proliferation, metastasis, and angiogenesis of gastric cancer through inhibition of the PI3K/AKT/mTOR pathway. 

    References:   Nat Chem Biol. 2008 Nov;4(11):691-9; Nat Med. 2010 Feb;16(2):205-13. 


    Customer Validation
    Official Supplier of
    • VE
    • OF
    • YALE
    • hhmi
    • 香港大学
    Related Products
    Publications Citing InvivoChem Products
    • Physicochemical and Storage Information
    • Protocol
    • Quality Control Documentation
    • Related Biological Data
    • Customer Review

    Molecular Weight (MW)

    308.34

    Formula

    C16H16N6O

    CAS No.

    1092351-67-1

    Storage

    -20℃ for 3 years in powder form

    -80℃ for 2 years in solvent

    Solubility (In vitro)

    DMSO: 62 mg/mL (201.1 mM)

    Water: <1 mg/mL

    Ethanol: 18 mg/mL (58.4 mM)

    Solubility (In vivo)

    2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5 mg/mL

    Other info

    Synonym: PP242; PP 242; PP-242

    Chemical Name: 2-(4-Amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol

    InChi Key: MFAQYJIYDMLAIM-UHFFFAOYSA-N

    InChi Code: InChI=1S/C16H16N6O/c1-8(2)22-16-13(15(17)18-7-19-16)14(21-22)12-6-9-5-10(23)3-4-11(9)20-12/h3-8,20,23H,1-2H3,(H2,17,18,19)

    SMILES Code: OC1=CC2=C(NC(C3=NN(C(C)C)C4=NC=NC(N)=C43)=C2)C=C1


    • Molarity Calculator
    • Dilution Calculator
    • The molarity calculator equation

      Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

      • Mass
      • Concentration
      • Volume
      • Molecular Weight *
      • =
      • ×
      • ×
    • The dilution calculator equation

      Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

      This equation is commonly abbreviated as: C1V1 = C2V2

      • Concentration (start)
      • ×
      • Volume (start)
      • =
      • Concentration (final)
      • ×
      • Volume (final)
      • ×
      • =
      • ×
      • C1
      •  
      • V1
      •  
      • C2
      •  
      • V2

    In Vitro

    Kinase Assay: In vitro mTOR (FRAP1) kinase assay: Recombinant mTOR is incubated with PP242 at 2-fold dilutions over a concentration range of 50-0.001 μM in an assay containing 50 mM HEPES, pH 7.5, 1 mM EGTA, 10 mM MgCl2, 0.01% Tween, 10 μM ATP (2.5 μCi of γ-32P-ATP), and 3 μg/mL BSA. Rat recombinant PHAS-1/4EBP1 (2 mg/mL) is used as a substrate. Reactions are terminated by spotting onto nitrocellulose, which is washed with 1 M NaCl/1% phosphoric acid (approximately 6 times, 5-10 minutes each). Sheets are dried and the transferred radioactivity quantitated by phosphorimaging. IC50 value is calculated by fitting the data to a sigmoidal dose-response curve using the Prism software package.

     

    Cell Assay: Cells (MEFs) are treated with increasing concentrations of PP242 for 72 hours in 96-well plates. After 72 hours of treatment, 10 μL of 440 μM resazurin sodium salt is added to each well, and after 18 hours, the florescence intensity in each well is measured using a top-reading florescent plate reader with excitation at 530 nm and emission at 590 nm.

    PP242 exhibits potent selectivity for mTOR over other PI3K family kinases such as p110α, p110β, p110γ, p110δ, and DNA-PK with IC50 of 1.96 μM, 2.2 μM, 1.27 μM, 0.102 μM, and 0.408 μM, respectively. PP242 displays some inhibitory activity against Ret, PKCα, PKCβ, and JAK2, while exhibits remarkable selectivity against 215 other protein kinases. Unlike rapamycin, PP242 inhibits both mTORC1 and mTORC2. In BT549 cells, PP242 treatment (0.04-10 μM) inhibits the phosphorylation of Akt, the mTOR substrate p70S6K, and its downstream target S6 in a dose-dependent manner. PP242 potently inhibits PKCα with IC50 of 49 nM. Low concentrations of PP242 inhibit the phosphorylation of Akt S473 and higher concentrations partially inhibit Akt T308-P in addition to S473-P. As PP242 is a more effective mTORC1 inhibitor than rapamycin, PP242 inhibits the proliferation of primary MEFs, and the phosphorylation of 4EBP1 at T36/45 and S65, more potently than rapamycin. PP242 but not rapamycin potently inhibits cap-dependent translation, by causing a higher level of binding between 4EBP1 and eIF4E than rapamycin. PP242 potently inhibits the proliferation of p190-transformed murine BM, SUP-B15, and K562 cells with GI50 of 12 nM, 90 nM, and 85 nM, respectively. PP242 also inhibits the growth of solid tumor cell lines such as SKOV3, PC3, 786-O, and U87 with GI50 of 0.49 μM, 0.19 μM, 2.13 μM, and 1.57 μM, respectively. PP242 is also more effective than rapamycin in achieving cytoreduction and apoptosis in multiple myeloma (MM) cells.

    In Vivo

    Administration of PP242 is able to completely inhibit the phosphorylation of Akt at S473 and T308 in fat and liver of mice. PP242 only partially inhibits the phosphorylation of Akt in skeletal muscle and is more effective at inhibiting the phosphorylation of T308 than S473, despite able to fully inhibit the phosphorylation of 4EBP1 and S6. Oral administration PP242 potently delays the leukemia onset in the mice model, and induces leukemia regression by inhibiting mTORC2 and mTORC1 activation that correlates with loss in cell size. PP242 treatment potently inhibits the growth of 8226 cells in mice

    Animal model

    Syngeneic (Balbc/J) mice with mouse p190-transformed BM cells to initiate leukemia, and female NSG mice injected (i.v.) with SUP-B15ffLuc cells or human Ph+ leukemia

    Formulation & Dosage

    Dissolved in PEG400; 60 mg/kg; Oral gavage

    References

    Nat Med. 2010 Feb;16(2):205-13; Nat Chem Biol. 2008 Nov;4(11):691-9. 


    These protocols are for reference only. InvivoChem does not independently validate these methods.

    Torkinib (PP242)

    Torkinib (PP242)

    PP242 selectively suppresses leukemic expansion in vivo and extends survival. Nat Med. 2010 Feb;16(2):205-13. 

    Torkinib (PP242)

    In vitro and in vivo selectivity of PP242 compared to rapamycin. Nat Med. 2010 Feb;16(2):205-13. 


    评论

      Home Prev Next Last page / pices

      发评论

      ×
      Your information is safe with us. * Required Fields.
      Products are for research use only;  We do not sell to patients
      Tel: 1-708-310-1919
      Fax: 1-708-557-7486
      Subscribe to our E-newsletter
      • Name*
      • *
      • E-mail*
      • *
      • instructions:
      • *
      Copyright 2020 InvivoChem LLC | All Rights Reserved
      prompt
      Do you confirm the receipt?