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Compound 401

CAS No. : 168425-64-7

MCE 国际站：Compound 401

产品活性：Compound 401 是一种合成的 DNA-PK (IC₅₀=0.28 μM) 抑制剂，在体外也靶向作用于 mTOR，但对 PI3K 没有抑制效果。

研究领域：Cell Cycle/DNA Damage  |  PI3K/Akt/mTOR

作用靶点：DNA-PK

In Vitro: Compound 401 is a potent inhibitor of DNA-PK (IC₅₀=0.28 μM). Compound 401 is reported to be a poor inhibitor of PI3K, ATM, and ATR in vitro, but it is active against mTOR. Compound 401 shows activity against mTOR (IC₅₀=5.3 μM) but not p110α/p85α PI3K (IC₅₀>100 μM). Treatment of cells with Compound 401 blocks the phosphorylation of sites modified by mTOR-Raptor and mTOR-Rictor complexes (ribosomal protein S6 kinase 1 Thr³⁸⁹ and Akt Ser⁴⁷³, respectively). By contrast, there is no direct inhibition of Akt Thr³⁰⁸ phosphorylation, which is dependent on PI3K. Similar effects are also observed in cells that lack DNA-PK. Compound 401 inhibits immunoprecipitated epitope-tagged mTOR or endogenous mTOR in Raptor immunoprecipitates. In both cases, inhibition of 67% or 78% is obtained at 5 μM or 10 μM Compound 401, respectively. By contrast, dose response curves show that the p110α/p85α or p110β/p85α PI3K complexes are poorly inhibited by Compound 401 at these concentrations. The proliferation of TSC1^-/- fibroblasts is inhibited in the presence of Compound 401, but TSC1^+/+ cells are resistant.

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