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

Description

Ceranib-2 is a ceramidase inhibitor that inhibits ceramidase activity (IC₅₀ = 28 μM in SKOV3 cells). It also increases intracellular accumulation of various ceramides, including C14 ceramide , C24 ceramide , C26 ceramide, and C26:1 ceramide, and total ceramide levels and decreases levels of dihydrosphingosine, sphingosine, and sphingosine-1-phosphate in SKOV3 cells. In vivo, ceranib-2 (20 and 50 mg/kg, i.p.) reduces tumor volume in a JC mammary adenocarcinoma mouse syngeneic tumor model.

Uses

Ceranib-2 is a potent and nonlipid ceramidase inhibitor that inhibits cellular ceramidase activity with an IC50 of 28 μM in SKOV3 cells. Ceranib-2 induces the accumulation of multiple ceramide species, decreases levels of sphingosine and sphingosine-1-phosphate (S1P), and induces cell apoptosis. Anticancer activity[1][2].

in vivo

References

[1] Draper JM, et al. Discovery and evaluation of inhibitors of human ceramidase. Mol Cancer Ther. 2011 Nov;10(11):2052-61. DOI:10.1158/1535-7163.MCT-11-0365
[2] Kus G, et al. Induction of apoptosis in prostate cancer cells by the novel ceramidase inhibitor ceranib-2. In Vitro Cell Dev Biol Anim. 2015 Nov;51(10):1056-63. DOI:10.1007/s11626-015-9932-9