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]. IC50 & Target: IC50: 28 μM (Ceramidase)^[1] In Vitro: 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]. In Vivo: 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].