NVP-231 (NVP231) is a potent, specific, and reversible ceramide kinase (CerK) inhibitor with IC50 of 12 nM. NVP-231 does not compete with ATP but rather with ceramide, displaying an inhibition constant (Ki) of 7.4 nM. NVP-231 inhibits C1P formation with IC50 of <10 nM in human CerK-overexpressing COS-cells (COS-CerK), achieved complete inhibition at 100 nM. NVP-231 also is a potent inhibitor of mouse CerK. NVP-231 does not inhibit sphingosine kinases and other lipid kinases, including phosphatidylinositol-3 kinase, phosphatidylinositol-4 kinase β, and Vps34. When combined with another ceramide metabolizing inhibitor, such as tamoxifen, NVP-231 synergistically increased ceramide levels and reduced cell growth.
