1. PI3K/Akt/mTOR
    Autophagy
  2. mTOR
    Autophagy

PP 242 

Cat. No.: HY-10474 Purity: 95.34%
Data Sheet SDS Handling Instructions

PP 242 is the first selective and ATP competitive mTOR inhibitor with IC50 of 8 nM.

For research use only. We do not sell to patients.
PP 242 Chemical Structure

PP 242 Chemical Structure

CAS No. : 1092351-67-1

Size Price Stock Quantity
10 mM * 1 mL in DMSO $55 In-stock
5 mg $50 In-stock
10 mg $65 In-stock
50 mg $130 In-stock
100 mg $220 In-stock
200 mg   Get quote  
500 mg   Get quote  

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    PP 242 purchased from MCE. Usage Cited in: Cancer Res. 2013 Apr 15;73(8):2574-86.

    Cells are treated with the indicated concentrations of AZD8055, Torin2 or staurosporin overnight and analyzed by western blot using antibodies specific for the indicated proteins.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    PP 242 is the first selective and ATP competitive mTOR inhibitor with IC50 of 8 nM.

    IC50 & Target

    IC50: 8 nM (mTOR), 100 nM (p110δ), 410 nM (DNA-PK), 410 nM (PDGFR)[1]

    In Vitro

    PP 242 (PP242) potently inhibits mTOR (IC50=8 nM) but is much less active against other PI3K family members. Testing of PP 242 against 219 protein kinases reveals remarkable selectivity relative to the protein kinome: at a concentration 100-fold above its IC50 for mTOR, PP 242 inhibits only one kinase by more than 90% (Ret) and only three by more than 75% (PKCα, PKCβII and JAK2V617F)[1]. PP 242 (PP242) has a dose-dependent effect on proliferation and at higher doses is much more effective than Rapamycin at blocking cell proliferation. The ability of PP 242 to block cell proliferation more efficiently than Rapamycin could be a result of its ability to inhibit mTORC1 and mTORC2, because Rapamycin can only inhibit mTORC1. In SIN1-/- MEFs, Rapamycin is also less effective at blocking cell proliferation than PP 242. That PP 242 and Rapamycin exhibit very different anti-proliferative effects in SIN1-/- MEFs suggests that the two compounds differentially affect mTORC1[2].

    In Vivo

    In fat and liver, PP 242 (PP242) is able to completely inhibit the phosphorylation of Akt at S473 and T308, consistent with its effect on these phosphorylation sites observed in cell culture. Surprisingly, PP 242 is only partially able to inhibit the phosphorylation of Akt in skeletal muscle and is more effective at inhibiting the phosphorylation of T308 than S473, despite it's ability to fully inhibit the phosphorylation of 4EBP1 and S6. These results will be confirmed by in vivo dose-response experiments, but, consistent with the partial effect of PP 242 on pAkt in skeletal muscle, a muscle-specific knockout of the integral mTORC2 component rictor resulted in only a partial loss of Akt phosphorylation at S473. These results suggest that a kinase other than mTOR, such as DNA-PK, may contribute to phosphorylation of Akt in muscle[2].

    References
    Preparing Stock Solutions
    Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
    1 mM 3.2432 mL 16.2159 mL 32.4317 mL
    5 mM 0.6486 mL 3.2432 mL 6.4863 mL
    10 mM 0.3243 mL 1.6216 mL 3.2432 mL
    Kinase Assay
    [1]

    Purified kinase domains are incubated with inhibitors at 2- or 4-fold dilutions over a concentration range of 50-0.001 µM or with vehicle (0.1% DMSO) in the presence of 10 µM ATP, 2.5 µCi of γ-32P-ATP and substrate. Reactions are terminated by spotting onto nitrocellulose or phosphocellulose membranes, depending on the substrate; this membrane is then washed 5-6 times to remove unbound radioactivity and dried. Transferred radioactivity is quantitated by phosphorimaging and IC50 values are calculated by fitting the data to a sigmoidal doseresponse using Prism software[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [2]

    PP 242 (PP242) is dissolved in DMSO and stored, and then diluted with appropriate media (DMSO 0.1%) before use[2].

    Wild-type and SIN1-/- MEFs are plated in 96-well plates at approximately 30% confluence and left overnight to adhere. The following day cells are treated with PP 242, Rapamycin, or vehicle (0.1% DMSO). After 72 h of treatment, 10 μL of 440 μM resazurin sodium salt is added to each well, and after 18 h, 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[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2]

    PP 242 (PP242) is prepared in 100 μL of vehicle containing 20% DMSO, 40% PEG-400, and 40% saline (Mice)[2].

    Mice[2]
    Six-wk-old male C57BL/6 mice are fasted overnight prior to drug treatment. PP 242 (0.4 mg), Rapamycin (0.1 mg), or vehicle alone is injected IP. After 30 min for the Rapamycin-treated mouse or 10 min for the PP 242 and vehicle-treated mice, 250 mU of insulin in 100 μL of saline is injected IP. 15 min after the insulin injection, the mice are killed by CO2 asphyxiation followed by cervical dislocation. Tissues are harvested and frozen on liquid nitrogen in 200 μL of cap lysis buffer. The frozen tissue is thawed on ice, manually disrupted with a mortar and pestle, and then further processed with a micro tissue-homogenizer. Protein concentration of the cleared lysate is measured by Bradford assay and 5-10 μg of protein is analyzed by Western blot. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    308.34

    Formula

    C₁₆H₁₆N₆O

    CAS No.

    1092351-67-1

    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

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

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