Ceramides have diverse roles in cell differentiation, proliferation, and apoptosis. Ceramide kinase converts ceramide to ceramide-1-phosphate (C1P), removing the effects of ceramide in favor of those directed by C1P. NVP-231 is a potent, reversible inhibitor of ceramide kinase (IC50 = 12 nM). It has minimal effect on several other lipid kinases, including sphingosine kinases 1 and 2. In cells in which exogenous short chain ceramide is converted to C1P, resulting in cell death, NVP-231 prevents both C1P synthesis and cell death. In mouse dermal microvascular endothelial cells, where ceramide kinase increases capillary-like tube formation, NVP-231 (100 nM) inhibits C1P formation as well as tube formation.
