Carmofur
 | |
| Systematic (IUPAC) name | |
|---|---|
|
5-fluoro-N-hexyl-2,4-dioxo-pyrimidine-1-carboxamide | |
| Clinical data | |
| AHFS/Drugs.com | International Drug Names |
| Routes of administration | Oral |
| Identifiers | |
| CAS Number |
61422-45-5  |
| ATC code | L01BC04 |
| PubChem | CID 2577 |
| DrugBank |
DB09010  |
| ChemSpider |
2479 |
| UNII |
HA82M3RAB2 |
| ChEMBL |
CHEMBL460499 |
| Synonyms | 1-hexylcarbamoyl-5-fluorouracil |
| Chemical data | |
| Formula | C11H16FN3O3 |
| Molar mass | 257.261 g/mol |
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Carmofur (INN) or HCFU (1-hexylcarbamoyl-5-fluorouracil) is a pyrimidine analogue used as an antineoplastic agent. It is a derivative of fluorouracil.
Mechanism of action
The expression of acid ceramidase (AC) – a cysteine amidase that hydrolyses the proapoptotic lipid ceramide – is abnormally high in several human tumors, which is suggestive of a role in chemoresistance. Available AC inhibitors lack, however, the potency and drug-likeness necessary to test this idea. Here we show that the antineoplastic drug carmofur, which is used in the clinic to treat colorectal cancers, is a potent AC inhibitor and that this property is essential to its anti-proliferative effects. Modifications in the chemical scaffold of carmofur yield new AC inhibitors that act synergistically with standard antitumoral drugs to prevent cancer cell proliferation. These findings identify AC as an unexpected target for carmofur, and suggest that this molecule can be used as starting point for the design of novel chemosensitizing agents. [1]
Uses
Colorectal Cancer
Carmofur, in its oral form, has also been used as adjuvant chemotherapy for curatively resected colorectal cancer patients. Trials and meta-analyses have confirmed that the drug is effective on patients with this cancer type, extending their survival.[2]
Adverse effects
As fluorouracil, carmofur has been known to induce leukoencephalopathy.[3][4][5]
References
- ↑ Realini, Natalia; Solorzano, Carlos; Pagliuca, Chiara; Pizzirani, Daniela; Armirotti, Andrea; Luciani, Rosaria; Paola Costi, Maria; Bandiera, Tiziano; Piomelli, Daniele (8 January 2013). "Discovery of highly potent acid ceramidase inhibitors with in vitro tumor chemosensitizing activity". Scientific Reports 3 (1035).
- ↑ Sakamoto, J; Hamada, C; Rahman, M; Kodaira, S; Ito, K; Nakazato, H; Ohashi, Y; Yasutomi, M (2005). "An Individual Patient Data Meta-analysis of Adjuvant Therapy with Carmofur in Patients with Curatively Resected Colon Cancer". Japanese Journal of Clinical Oncology 35 (9): 536–544. doi:10.1093/jjco/hyi147. PMID 16155120.
- ↑ Yamada T, Okamura S, Okazaki T; et al. (June 1989). "Leukoencephalopathy following treatment with carmofur: a case report and review of the Japanese literature". Asia Oceania J Obstet Gynaecol 15 (2): 161–8. PMID 2667512.
- ↑ Mizutani T (February 2008). "[Leukoencephalopathy caused by antineoplastic drugs]". Brain Nerve (in Japanese) 60 (2): 137–41. PMID 18306661.
- ↑ Baehring JM, Fulbright RK (May 2008). "Delayed leukoencephalopathy with stroke-like presentation in chemotherapy recipients". J Neurol Neurosurg Psychiatr 79 (5): 535–9. doi:10.1136/jnnp.2007.123737. PMID 17682013.
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