BAY1082439

BAY1082439 is an orally bioavailable, selective PI3Kα/β/δ inhibitor. BAY1082439 also inhibits mutated forms of PIK3CA. BAY1082439 is highly effective in inhibiting Pten-null prostate cancer growth[1][2].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> PI3K/Akt/mTOR >> PI3K

PI3Kα

PI3Kβ

PI3Kδ

BAY1082439 is a highly selective PI3Kα/α-balanced inhibitor. BAY1082439 has an IC50 ratio of 1:3 in biochemical assays of PI3Kα (4.9 nM) vs. PI3Kα (15.0 nM), and >1000-fold selectivity against mTOR kinase[1]. BAY1082439 (0.1-1 μM; 72 hours) is more effective than PI3Kα- and/or PI3Kβ-selective inhibitors in blocking PTEN-null prostate cancer cells[2]. Cell Viability Assay[2] Cell Line: PC3 and LNCaP cells (PTEN-null human prostate cancer cell lines) Concentration: 0.1, 0.33, 1, 3.3, 10 μM Incubation Time: 72 hours Result: Efectively inhibited cell growth by blocking the G1/S cell cycle transition and by inducing apoptosis.

BAY1082439 (75 mg/kg; p.o.; daily for 4 weeks) is effective in preventing Pten-null prostate cancer progression[2]. Animal Model: Pten conditional knockout mouse model (Pb-Cre+;PtenL/L, CP model)[2] Dosage: 75 mg/kg Administration: P.o.; daily for 4 weeks Result: Significantly decreased tumor size and P-AKT staining, nearly normal luminal architecture, and a significant reduction of Ki67-positive cells. Significantly inhibit the human prostate cancer growth.

[1]. Ningshu Liu, et al. Abstract 2799: BAY 1082439, a highly selective and balanced PI3Kα/β inhibitor demonstrated potent activity in tumors with activated PI3Kα and loss-of-function of PTEN. Abstract nr 2799. doi:1538-7445.AM2012-2799.

[2]. Yongkang Zou, et al. Co-Targeting the Cell Intrinsic and Microenvironment Pathways of Prostate Cancer by PI3Kα/β/δ inhibitor BAY1082439. Mol Cancer Ther. 2018 Oct;17(10):2091-2099.