Clinical data | |
---|---|
Other names | 1-hexylcarbamoyl-5-fluorouracil, HCFU, N-hexylcarbamoyl-5-fluorouracil, Yamaful, NCGC00095165-01, Hexylcarbamoyl fluorouracil, 61422-45-5, UNII-HA82M3RAB2, CCRIS 2759, C11H16FN3O3, Uracil, 5-fluoro-1-hexylcarbamoyl-, BRN 0888898, HA82M3RAB2, 1(2H)-Pyrimidinecarboxamide, 5-fluoro-N-hexyl-3,4, |
AHFS/Drugs.com | International Drug Names |
Routes of administration | Oral |
ATC code | |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.216.315 |
Chemical and physical data | |
Formula | C11H16FN3O3 |
Molar mass | 257.265 g·mol−1 |
3D model (JSmol) | |
| |
| |
(what is this?) (verify) |
Carmofur (INN) or HCFU (1-hexylcarbamoyl-5-fluorouracil) is a pyrimidine analogue used as an antineoplastic agent. It is a derivative of fluorouracil, being a lipophilic-masked analog of 5-FU that can be administered orally.[1]
Carmofur prodrug is ingested and taken up in the intestine, overcoming the problem of 5-FU degradation by dihydropyrimidine dehydrogenase. Once inside a cell, the carmofur prodrug is converted into 5-FU.
The mechanism of action of carmofur prodrug is traditionally thought to be the generation of 5–FU.[2] However, carmofur is a highly potent acid ceramidase (AC) inhibitor.[2] Ceramide influences cancer cell survival, growth and death.[2] Inhibition of AC activity sensitizes tumor cells to the effects of antineoplastic agents and radiation.[2] Carmofur, much more effective than temozolomide, has been reported as the small-molecule drug capable of killing adult and pediatric glioblastomas.[3][4]
Product marketing for carmofur started in 1981. Carmofur has also been used as adjuvant chemotherapy for curatively resected colorectal cancer patients in China, Japan, and Finland for many years.[5] Trials and meta-analyses have confirmed that the drug is effective on patients with this cancer type, extending their survival.[6]
Carmofur has been shown to inhibit the SARS-CoV-2 main protease, and is therefore a promising lead compound to develop new antiviral treatment for COVID-19.[7]
As fluorouracil, carmofur has been known to induce leukoencephalopathy, characterized by progressive damage to white matter in the brain with stroke-like symptoms.[8][9][10]
A clinical trial for small hepatocellular carcinoma was stopped prematurely because 56% of the treated patients had unacceptable side effects. Moreover, the treatment had no survival advantage for stage 1 and 2 cancer patients.[11] This may be a reason why carmofur was never pursued for FDA-approval in the US.[1]
Ozaki et al. have reported a synthesis by treating 5-FU with phosgene and hexylamine.[12] Xiong et al. reported an alternative approach for the synthesis of carmofur . Chemical preparations and structures can be found here.[1]