Molecular Formula | C33H29N7O |
Molar Mass | 539.63 |
Storage Condition | 2-8℃ |
In vitro study | Consistent with the allosteric mode of inhibition, Akt1 and Akt2-IN-1 (Compound 17) is dependent on the PH-domain for Akt inhibition, is selective for Akt1/2 over Akt3 (IC 50 =1900 nM), and is highly selective over other members of the AGC family of kinases (>50 μM vs PKA, PKC, SGK). Akt1 and Akt2-IN-1 (Compound 17) has moderate activity in an hERG binding assay (IC 50 =5610 nM) and is a substrate for human P-glycoprotein. |
In vivo study | Akt1 and Akt2-IN-1 (Compound 17) is well tolerated in at exposures that provide high levels of Akt1 and 2 inhibition in vivo. Akt1 and Akt2-IN-1 (Compound 17) has also been shown to inhibit the growth of A2780 tumors in vivo when used as monotherapy. Akt1 and Akt2-IN-1 (Compound 17) has potent inhibitory activity against Akt1 and 2 in vivo in a mouse lung and efficacy in a tumor xenograft model. Akt1 and Akt2-IN-1 (Compound 17) 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 and Akt2-IN-1 (Compound 17), 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 and Akt2-IN-1 (Compound 17) is well tolerated in mice and shows high levels of Akt inhibition in mouse lung. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 1.853 ml | 9.265 ml | 18.531 ml |
5 mM | 0.371 ml | 1.853 ml | 3.706 ml |
10 mM | 0.185 ml | 0.927 ml | 1.853 ml |
5 mM | 0.037 ml | 0.185 ml | 0.371 ml |
biological activity | Akt1 and Akt2-IN-1 are potent allosteric inhibitors of Akt1 (IC50=3.5 nM) and Akt2 (IC50=42 nM). |