| Description: |
Akt1 and Akt2-IN-1 is an allosteric inhibitor of Akt1 (IC50 = 3.5 nM) and Akt2 (IC50 = 42 nM), with potent and balanced activity.in vitro: Akt1 and Akt2-IN-1 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 lM vs PKA, PKC, SGK). Akt1 and Akt2-IN-1 has moderate activity in an hERG binding assay (IC50 = 5610 nM) and is a substrate for human P-glycoprotein (MDR1 Directional Transport Ratio (B to A/A to B) = 17.6). Akt1 and Akt2-IN-1 also shows good physical properties with a human plasma protein binding of 97.3% and a logP = 3.51.
in vivo: Akt1 and Akt2-IN-1 has potent inhibitory activity against Akt1 and Akt 2 in vivo in a mouse lung and efficacy in a
tumor xenograft model. Akt1 and 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. |
