FIGURE 1.

Validation of novel PI3K class IA isoform-selective inhibitors. A, growth IC₅₀ values for MLN1117 and GDC-0941 in a panel of breast cancer cell lines harboring a PTEN-null mutation, compared with lines with either a p110α mutation or HER2 overexpression. B, phosphorylation status of Akt in response to either MLN1117 or GDC-0941 in three different cell lines harboring the mutations described above. C, cell lines (5000 cells/well) either harboring a constitutively activating p110α H1047R mutation (SK-OV-3) or PTEN deletion (U87MG) were cultured under low serum (0.2% FBS) conditions for 48 h in the presence of the indicated inhibitors (2-fold dilution series from right to left: 2, 1, 0.5, 0.25, and 0.125 μm). MTS conversion assay was used to measure viable cell numbers relative to vehicle-treated control (100%) (background-subtracted). Data represent mean ± S.E. of n = 3 to 5 experiments (*, p < 0.05; **, p < 0.01; #, p < 0.001, repeated-measures analysis of variance, measured versus the vehicle-treated control).