3-[3-(4-Methoxyphenyl)-1-oxo-2-propen-1-yl]-4-phenyl-2(1H)-quinolinone

Ceramidase catalyzes the hydrolysis of the N-acyl linkage between the fatty acid and sphingosine base in ceramide to produce sphingosine and a free fatty acid. It plays a critical role in regulating cell fate and its inhibition in both malignant and non-cancerous cells leads to apoptosis. Ceranib-2 is a non-lipid inhibitor of cellular ceramidase activity that demonstates an IC50 of 28 μM in a cell-based assay. At 3.125 μM, Ceranib-2 increased the accumulation of endogenous ceramide species by 109% compared to controls and dose-dependently decreased intracellular levels of sphingosine and sphingosine-1-phosphate. Ceranib-2 inhibited cell proliferation of SKOV3 ovarian cancer cells with an IC50 value of 0.71 μM and had additive effects on cell proliferation when combined with paclitaxel. In vivo, Ceranib-2 at 20-50 mg/kg supresses tumor growth in a syngeneic tumor model without noticeable toxicity.