Ceranib-2

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].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> GPCR/G Protein >> LPL Receptor

IC50: 28 μM (Ceramidase)[1]

Ceranib-2 (10 nM-10 µM; 72 hours; SKOV3 cells) treatment inhibits cell proliferation and/or survival with an IC50 value of 0.73 μM[1]. Ceranib-2 (0.75-1.5 µM; 48 hours; SKOV3 cells) treatment causes accumulation of cells in the sub-G1 (apoptosis), G2 and S (0.75 μM only) phases of the cell cycle, concomitant with reductions in the number of cells in G1 phase[1]. Ceranib-2 produces a dose-dependent decrease in ceramidase activity, with 50% inhibition at 28 μM, induces the accumulation of multiple ceramide species, and decreases levels of sphingosine and S1P[1]. Cell Proliferation Assay[1] Cell Line: SKOV3 cells Concentration: 10 nM-10 µM Incubation Time: 72 hours Result: Cell proliferation and/or survival were inhibited with an IC50 value of 0.73 μM for Ceranib-2. Cell Cycle Analysis[1] Cell Line: SKOV3 cells Concentration: 0.75 μM, or 1.5 μM Incubation Time: 48 hours Result: Induced cell-cycle arrest and cell death.

Ceranib-2 (20-50 mg/kg; intraperitoneal injection; daily for 5 days per week; for 3 weeks; female Balb/c mice) treatment delays tumor growth in a syngeneic tumor model without hematologic suppression or overt signs of toxicity[1]. Intraperitoneal administration of 50 mg/kg Ceranib-2 results in progressive increases in its circulating levels, reaching a peak plasma concentration of approximately 40 μM at the 2 hr time point. Ceranib-2 appears to be cleared with a half-life of less than 2 hr[1]. Animal Model: Female Balb/c mice injected with JC murine mammary adenocarcinoma cells[1] Dosage: 20 mg/kg or 50 mg/kg Administration: Intraperitoneal injection; daily for 5 days per week; for 3 weeks Result: Delayed tumor growth in a syngeneic tumor model.

[1]. Draper JM, et al. Discovery and evaluation of inhibitors of human ceramidase. Mol Cancer Ther. 2011 Nov;10(11):2052-61.

[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.