PF-04691502 is a potent, ATP competitive, dual inhibitor of PI3K and mTOR. It selectively inhibits human PI3K isoforms α, β, δ, and γ (Kis = 1.8, 2.1, 1.6, and 1.9 nM, respectively) and human mTOR (Ki = 16 nM) without significantly inhibiting a panel of more than 80 related protein kinases at concentrations up to 10 μM. PF-04691502 inhibits cell proliferation of BT20 (breast), SKOV3 (ovarian), and U87MG (glioblastoma) cancer cells with IC50 values of 313, 188, and 179 nM, respectively, and shows good in vivo efficacy in U87MG, SKOV3, and four separate non-small cell lung cancer xenograft mouse models. PF-04691502 has been used to inhibit activation of PI3K and mTOR effector kinases and prevent a p27-dependent increase in cell motility and invasion in a highly bone-metastatic model of breast cancer.
