BAY-1082439 is an inhibitor of PI3Kα, PI3Kβ, and PI3Kδ (IC50s = 5, 15, and 1 nM, respectively).1 It is selective for PI3Kα, -β, and -δ over PI3Kγ (IC50 = 52 nM). BAY-1082439 selectively inhibits proliferation of PTEN-null LNCaP and PC3 prostate cancer cells over wild-type PTEN isogenic PC3 cells. BAY-1082439 (75 mg/kg) decreases intratumoral levels of phosphorylated Akt and reduces tumor growth in a mouse model of castration-resistant prostate cancer using castrated Pten conditional knockout mice (Pten-null mice). Intermittent administration of BAY-1082439 (180 mg/kg) reverses resistance to an anti-PD-1 antibody and induces CD8+ T cell clonal expansion and T cell-mediated inflammation in the tumor microenvironment in castrated Pten-null mice.2
1.Zou, Y., Qi, Z., Guo, W., et al.Cotargeting the cell-intrinsic and microenvironment pathways of prostate cancer by PI3Kα/β/δ inhibitor BAY1082439Mol. Cancer Ther.17(10)2091-2099(2018) 2.Qi, J., Xu, Z., Zhang, L., et al.Overcoming resistance to immune checkpoint therapy in PTEN-null prostate cancer by intermittent anti-PI3Kα/β/δ treatmentNat. Commun.13(1)182(2022)