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mTOR inhibitor-3

CAS No. : 1207358-59-5

MCE 国际站：mTOR inhibitor-3

产品活性：mTOR inhibitor-3 是一种有效的 mTOR 抑制剂，K_i 值为 1.5 nM。mTOR inhibitor-3 在细胞实验及体内药代动力学 (PK)/药效学 (PD) 实验中都抑制 mTORC1 和 mTORC2。

研究领域：PI3K/Akt/mTOR

作用靶点：mTOR

In Vitro: mTOR inhibitor-3 (Compound 12i) inhibits mTOR with a K_i of 1.5 nM, 500-fold selectivity over closely related PI3 kinases. mTOR inhibitor-3 inhibits NCI-PC3 and MCF7neo/Her2 cells proliferation with IC₅₀s of 150 nM and 57 nM, respectively.

In Vivo: mTOR inhibitor-3 (Compound 8h) has high free plasma clearance in both mice (1818 mL/min/kg) and rats (1538 mL/min/kg in rat) . mTOR inhibitor-3 (Compounds 12i) is selected for this study due to its potency, selectivity, and favorable mouse PK profile. Plasma levels of mTOR inhibitor-3 6 h following oral administration in PC3 tumor-bearing mice along with the fold decreases of phosphorylated mTORC1 and -2 substrates relative to time-matched vehicle controls. mTOR inhibitor-3 has moderate terminal elimination half-life (t_1/2=1.7 h for mouse(1 mg/kg, iv)). mTOR inhibitor-3 achieves tumor stasis at the highest 200 mg/kg/day dose examined, which appears to also be approaching the limit of tolerability for this molecule.

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