Description
A PI3Kα inhibitor (Ki = 0.034 nM); selective for PI3Kα over PI3Kβ, PI3Kδ, and PI3Kγ (Kis = 99.7, 12.2, and 18.2 nM, respectively) and is 4.4-fold selective in decreasing the phosphorylated levels of PRAS40 in HCC1954 cells, which express wild-type p110α and p110αH1047R, over HDQ-P1 cells, which only express wild-type p110α; induces PARP cleavage, a marker of apoptosis, in HCC1954 cells at 111 nM; reduces the levels of phosphorylated Akt and PRAS40 and the levels of mutant p110α in HCC1954 cells, but not HDQ-P1 cells, at 111, 333, and 1,000 nM; decreases tumor volume in an HCC1954 mouse xenograft model at 25 or 50 mg/kg per day