Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092
Fig 4
Comparison of AKT pathway inhibition by ARQ 092, ARQ 751, MK-2206, and GDC-0068 in MDA-MB-453, NCI-H1650, and KU-19-19 cells.
(A) MDA-MB 453 breast cancer cell line (PIK3CAH1047R; Her2 amp), (B) NCI-H1650 NSCLC cell line (PTEN null), and (C) KU-19-19 bladder cancer cell line (AKT1-E17K&E49K; NRas Q61R) were treated with various concentrations (1 = 0, 2 = 0.012, 3 = 0.037, 4 = 0.11, 5 = 0.33, and 6 = 1 μM) of ARQ 092, ARQ 751, MK-2206 or GDC-0068 for 2 hours. pAKT(S473), pAKT(T308), pPRAS40(T246), pFOXO1(T24) /3a(T36), pGSK3β(S9), pAS160(S318), pBAD(S136), pS6(S235/236) and p4E-BP1(S65) and phospho ERK were assessed by western blot analysis.