362003-83-6

NVP-231 is a potent, specific, and reversible CerK inhibitor(IC50=12±2 nM) that competitively inhibits binding of ceramide to CerK.IC50 Value: 12±2 nM [1]Target: CERKin vitro: NVP-231 showed an IC50 value of 12 ± 2 nM and 90% inhibition at 100 nM in the radioassay. NVP-231 did not compete with ATP but rather with ceramide, displaying an inhibition constant (Ki) of 7.4 nM. Furthermore, inhibition by NVP-231 was instantaneous and fully reversible, implying that this compound does not covalently modify CerK. At 10 nM, NVP-231 inhibited C1P formation by >50%; at 100 nM, NVP-231 achieved complete inhibition. Thus the potency and efficacy of NVP-231 observed in cell culture are consistent with those found in vitro. It is noteworthy that, NVP-231 did not inhibit GlcCer and SM formation; rather, it increased these metabolites in correlation with compound concentration, demonstrating that NVP-231 does not act as a general inhibitor of ceramide metabolism [1]. The EC(50) of NVP-231 in this assay is in the low nanomolar range, consistent with the IC(50) determined in activity assays in vitro using purified CerK [2].