WYE-354,1062169-56-5

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WYE-354

CAS No. : 1062169-56-5

MCE 国际站：WYE-354

产品活性：WYE-354 是一种 ATP 竞争性的 mTOR 抑制剂，IC₅₀ 为 5 nM。WYE-354 也抑制 PI3Kα 和 PI3Kγ，IC₅₀ 分别为 1.89 μM 和 7.37 μM。WYE-354 抑制 mTORC1 和 mTORC2。WYE-354 在体外能诱导自噬 (autophagy) 激活.

研究领域：PI3K/Akt/mTOR  |  Autophagy  |  Apoptosis

作用靶点：mTOR  |  Autophagy  |  Apoptosis

In Vitro: In the DELFIA measuring His6-S6K1 T389 phosphorylation, WYE-354 inhibits recombinant mTOR enzyme with an IC₅₀ of 5 nM. Cell viability is analyzed by MTS assay. G-415 and TGBC-2TKB cell lines are treated with increasing concentrations of WYE-354 (0.1, 1, 5 and 10 μM) for 24, 48, and 72 hours. WYE-354 significantly reduces cell viability starting at a 1 μM concentration after a 24 hours exposure, in both studied cell lines (P<0.001). A decrease in cell viability is not observed at a dose of 100 nM, except for the TGBC-2TKB cell line after 72 hours of treatment.

In Vivo: The effect of Rapamycin and WYE-354 on tumor growth is evaluated in xenograft GBC tumor models. 2×10⁶ or 5×10⁶ cells of G-415 or TGBC2TKB, respectively, are xenotransplanted into NOD-SCID mice subcutaneously. When tumors reach an average volume of 100 mm³, the mice are treated either with Rapamycin or WYE354. Rapamycin is administered i.p. at a concentration of 10 mg/kg, daily for 5 days per week for 3 weeks, while WYE-354 is administrated at a daily i.p. dose of 50 mg/kg for 5 days. Mice are sacrificed 30 days after the initiation of the treatments and an autopsy is performed that include removal of the entire tumor area. Mice treated with WYE-354 exhibit 68.6% and 52.4% reduction in average tumor size (P<0.01; P<0.01), as well as 82.9% and 45.5% (P<0.01; ns) reduction in tumor weight, respectively.

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