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Akt1/Akt2-IN-1

CAS No. : 893422-47-4

MCE 国际站：Akt1/Akt2-IN-1

产品活性：Akt1/Akt2-IN-1 (Compound 17) 是一种有效的变构抑制剂，抑制 Akt1 (IC₅₀=3.5 nM) 和 Akt2 (IC₅₀=42 nM)。

研究领域：PI3K/Akt/mTOR

作用靶点：Akt

In Vitro: Consistent with the allosteric mode of inhibition, Akt1/Akt2-IN-1 (Compound 17) is dependent on the PH-domain for Akt inhibition, is selective for Akt1/2 over Akt3 (IC₅₀=1900 nM), and is highly selective over other members of the AGC family of kinases (>50 μM vs PKA, PKC, SGK). Akt1/Akt2-IN-1 has moderate activity in an hERG binding assay (IC₅₀=5610 nM) and is a substrate for human P-glycoprotein.

In Vivo: Akt1/Akt2-IN-1 (Compound 17) is well tolerated in at exposures that provide high levels of Akt1 and 2 inhibition in vivo. Akt1/Akt2-IN-1 has also been shown to inhibit the growth of A2780 tumors in vivo when used as monotherapy. Akt1/Akt2-IN-1 has potent inhibitory activity against Akt1 and 2 in vivo in a mouse lung and efficacy in a tumor xenograft model. Akt1/Akt2-IN-1 shows good pharmacokinetics in rat with a low clearance of 4.6 mL/min/kg and a half-life of 3.8 h. Due to the improved cell potency, physical properties, and rodent pharmacokinetics of Akt1/Akt2-IN-1, tolerability and Akt inhibition are assessed in mice. Using an acute dosing schedule (IP dosing of 50 mg/kg at times 0, 3, and 8 h), administration of Akt1/Akt2-IN-1 is well tolerated in mice and shows high levels of Akt inhibition in mouse lung.

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