893422-47-4

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). It has moderate activity in an hERG binding assay (IC ₅₀ =5610 nM) and is a substrate for human P-glycoprotein.

Akt1 and Akt2-IN-1 (Compound 17) is well tolerated in at exposures that provide high levels of Akt1 and 2 inhibition in vivo. It 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. And it shows good pharmacokinetics in rat with a low clearance of 4.6 mL/min/kg and a half-life of 3.8 h.