IPI-9119 is an orally active, selective and irreversible FASN inhibitor with an IC50 of 0.3 nM in vitro biochemical assay. IPI-9119 inhibits tumor growth of castration-resistant prostate cancer (CRPC) xenografts mouse models[1][2].
IPI-9119 inhibits FASN in cellular occupancy assays (IC50∼10nM), and shows more than 400-fold selectivity against several additional serine hydrolases[2]. IPI-9119 (0.1-0.5 μM; 6 days) inhibits cell growth and induces cell cycle arrest, apoptosis[1]. IPI-9119 (0.05-5 μM; 6 days) inhibits AR-FL and AR-V7 protein expression[1].
IPI-9119 (SC pump infusion; 0.5 μL/h; 100 mg/mL; for 28 days) inhibits tumor growth of CRPC xenografts mouse models[1].
[1]. Giorgia Zadra, et al. Inhibition of de novo lipogenesis targets androgen receptor signaling in castration-resistant prostate cancer. Proc Natl Acad Sci U S A. 2019 Jan 8;116(2):631-640.
[2]. Erin Broph, et al. Abstract 1891: Pharmacological target validation studies of fatty acid synthase in carcinoma using the potent, selective and orally bioavailable inhibitor IPI-9119.