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Vistusertib

CAS No. : 1009298-59-2

MCE 国际站：Vistusertib

产品活性：Vistusertib (AZD2014) 是一种ATP竞争性的 mTOR 抑制剂，IC₅₀ 为 2.81 nM。AZD2014 抑制 mTORC1 和 mTORC2 复合物。

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

作用靶点：mTOR  |  Autophagy  |  Apoptosis

In Vitro: The inhibitory effects of Vistusertib (AZD2014) are measured against isolated recombinant mTOR enzyme (IC₅₀ of 2.81 nM) as well as in cellular assays measuring both mTORC1 and mTORC2 activities. In MDAMB468 cells, Vistusertib (AZD2014) decreases the phosphorylation of the mTORC1 substrate ribosomal protein S6 (Ser235/236) with a mean IC₅₀ value of 210 nM and the mTORC2 substrate AKT (Ser473) with a mean IC₅₀ value of 78 nM.

In Vivo: Vistusertib (AZD2014) induces dose-dependent tumor growth inhibition in several xenograft and primary explant models. The antitumor activity of Vistusertib (AZD2014) is associated with modulation of both mTORC1 and mTORC2 substrates, consistent with its mechanism of action. The pharmacokinetics of Vistusertib (AZD2014) in mice is tested upon administration of doses between 7.5 and 15 mg/kg. A dose-dependent increase in C_max and AUC is observed following single dose and repeat dosing of AZD2014: C_max range from 1 to 16 μM and AUC range from 220 to 5,042 μM·h across this dose range. The pharmacodynamic effect of Vistusertib (AZD2014) against an mTORC1 biomarker (phosphorylation of S6) and an mTORC2 biomarker (phosphorylation of AKT) is assessed in SCID mice bearing MCF7 xenografts following administration of 3.75, 7.5, and 15 mg/kg AZD2014. There is a good relationship between the drug plasma concentrations and biomarker levels (estimated p-AKT IC₅₀ of 0.119 μM total, 53% SE, and estimated p-S6 IC₅₀ 0.392 μM, 28.8% SE).

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