Carmofur is an inhibitor of acid ceramidase (IC
50 = 79 nM for the rat enzyme) and a derivative of 5-flurouracil (Item No.
14416).
1 It reduces acid ceramidase activity in a dose- and time-dependent manner and induces intracellular accumulation of various ceramide species, including C18 ceramide (Item No.
19556), C16 ceramide (Item No.
24426), and C14 ceramide (Item No.
22531) in SW403 colon and LNCaP prostate cancer cells. Carmofur induces apoptosis in SW403 cells without inhibiting DNA synthesis (IC
50 = 1,212 mM for human thymidylate synthetase). It also reduces acid ceramidase activity and increases ceramide accumulation in mouse lung and brain when administered at doses of 10 and 30 mg/kg.