| 产品介绍 |
PP242 is a highly potent, selective and ATP-competitive mTORC1/mTORC2 inhibitor (IC50 = 8 nM). It has > 10 folds selectivity over the other PI-3K family kinases (IC50 0.102 μM, 0.408 μM, 1.27 μM, 1.96 μM and 2.2 μM for p110γ, DNA-PK, p110δ, p110α and p110β, respectively). Except some weak inhibitory activity against PKCα, JAK2, PKCβI, PKCβII and RET (0.05-0.22 μM), PP242 exhibits excellent selectivity over 215 other protein kinases. PP242 differentially inhibits insulin-stimulated phosphorylations of cellular proteins both in vitro and in vivo in a manner distinctly different from that seen in mTORC2-functional knockout SIN1-/- cells or in cultures treated with Rapamycin, which targets only mTORC1, but not mTORC2. Blockage of 4EBP1 T36/T45/S65 phosphorylation by PP242 upon insulin stimulation in primary MEFs correlates well with an enhanced 4EBP1 association with the cap-binding protein eIF4E, resulting in a selective inhibition of cap-dependent, but not cap-independent, protein translation.
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