Ceramide kinase (CerK), which belongs to the diacylglycerol kinase superfamily, produces the bioactive lipid ceramide-1-phosphate (C1P) and appears as a key enzyme for controlling ceramide levels. NVP-231 is a potent, specific, and reversible CerK inhibitor that competitively inhibits binding of ceramide to CerK with an IC50 value of 12 nM. At 10 nM, NVP-231 inhibited C1P formation by 50%; at 100 nM, NVP-231 achieved complete inhibition in human CerK-overexpressing COS-cells. Similar drop could also be found in mouse peritoneal macrophages and mouse bone marrow-derived mast cells[3]. When treating either MCF-7 or NCI-H358 cells with NVP-231 for 48h, viability was concentration-dependently reduced with an IC50 of about 1 μM in MCF-7 cells and 500 nM in NCI-H358 cells. Further, 1 μM NVP-231 caused a 60–70% reduction of DNA synthesis after 72h in both cell lines. Moreover, cell cycle analysis revealed that NVP-231 (24h treatment with increasing concentrations) decreased the number of cells in S phase and induced M phase arrest with an increased mitotic index[4].
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