NVP 231 is a potent, specific, and reversible ceramide kinase (CerK) inhibitor(IC₅₀=12 nM) that competitively inhibits binding of ceramide to CerK^[1]. NVP 231 induces cell apoptosis by increasing DNA fragmentation and caspase-3 and caspase-9 cleavage^[2]. IC50 & Target: IC50: 12 nM (CerK); apoptosis^[1][3] In Vitro: NVP-231 (0-500 nM; 24 hours) gradually reduces the cellular CerK activity, as measured by NBD-C1P formation, demonstrating that NVP-231 active in transfected cells. The IC₅₀ for CerK in this cellular system is 59.70 ± 12 nM^[3].
NVP-231 (0-1000 nM; 48 hours) decreases cell viability as a dose-dependent manner. This compound shows IC₅₀ values of 1 μM in MCF-7 cells and 500 nM in NCI-H358 cells^[3].
NVP-231 (1 μM; 24-72 hours) induces caspase-3 and caspase-9 cleavage in both cell lines. However, the highest caspase-3 and caspase-9 cleavage and activation occurred at 24 hours in MCF-7 cells, then decreases again. In NCI-H358 cells, caspase-3 and caspase-9 cleavage occurrs continuously over 72 hours^[3].
NVP-231 (0-500 nM; 24 hours) causes a concentration-dependent up-regulation of cyclin B1 phosphorylation at Ser133 and a reduction of CDK1 phosphorylation at Tyr15. The total CDK1 expression also declined upon CerK inhibition^[3].