TY - JOUR T1 - Targeting Ceramide Metabolism with a Potent and Specific Ceramide Kinase Inhibitor JF - Molecular Pharmacology JO - Mol Pharmacol SP - 925 LP - 932 DO - 10.1124/mol.108.048652 VL - 74 IS - 4 AU - Christine Graf AU - Martin Klumpp AU - Michael Habig AU - Philipp Rovina AU - Andreas Billich AU - Thomas Baumruker AU - Berndt Oberhauser AU - Frédéric Bornancin Y1 - 2008/10/01 UR - http://molpharm.aspetjournals.org/content/74/4/925.abstract N2 - Ceramide kinase (CerK) produces the bioactive lipid ceramide-1-phosphate (C1P) and appears as a key enzyme for controlling ceramide levels. In this study, we discovered and characterized adamantane-1-carboxylic acid (2-benzoylamino-benzothiazol-6-yl)amide (NVP-231), a potent, specific, and reversible CerK inhibitor that competitively inhibits binding of ceramide to CerK. NVP-231 is active in the low nanomolar range on purified as well as cellular CerK and abrogates phosphorylation of ceramide, resulting in decreased endogenous C1P levels. When combined with another ceramide metabolizing inhibitor, such as tamoxifen, NVP-231 synergistically increased ceramide levels and reduced cell growth. Therefore, NVP-231 represents a novel and promising compound for controlling ceramide metabolism that may provide insight into CerK physiological function. The American Society for Pharmacology and Experimental Therapeutics ER -