Description
Carmofur is an inhibitor of acid ceramidase (IC
50 = 79 nM for the rat enzyme) and a derivative of 5-flurouracil . It reduces acid ceramidase activity in a dose- and time-dependent manner and induces intracellular accumulation of various ceramide species, including C18 ceramide , C16 ceramide , and C14 ceramide 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.
Originator
Mifurol,Mitsui,Japan,1981
Uses
Carmofur has been used as an inhibitor of acid ceramidase to study its effects on glucosylsphingosine (GlcSph) production in human embryonic kidney 293T (HEK293T) cells. It has also been used as an inhibitor of acid ceramidase to study its effects on acid‐mediated hydrolysis of ceramide which kicks-in consumption and the generation of sphingosine .
Definition
ChEBI: Carmofur is an organohalogen compound and a member of pyrimidines.
Manufacturing Process
13.0 g (0.10 mol) of 5-fluorouracil was suspended in 60 ml of dimethyl
acetamide, then 14.0 g (0.11 mol) of n-hexyl isocyanate was added thereto at
room temperature and stirred at 50°C for 8 hours. After the reaction mixture
was concentrated under reduced pressure, the residue was poured into 400 ml
of water and resultant precipitate was filtered off. The precipitate was washed
and dried and 19.3 g (75.0% yield) of 5-fluoro-1-(n-hexylcarbamoyl)uracil
was obtained.
The product was recrystallized from ether and there were obtained white
crystals melting at 283°C (decomposition).
Therapeutic Function
Antineoplastic
Biochem/physiol Actions
Carmofur is a derivative of fluorouracil, an antimetabolite used as an antineoplastic agent.
