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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 |
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ECHA InfoCard | 100.216.315 |
Chemical and physical data | |
Formula | C11H16FN3O3 |
Molar mass | 257.265 g·mol−1 |
3D model (JSmol) | |
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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, 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]
Chemotherapy is the type of cancer treatment that uses one or more anti-cancer drugs in a standard regimen. Chemotherapy may be given with a curative intent, or it may aim only to prolong life or to reduce symptoms. Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology.
Fluorouracil, sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancreatic cancer, breast cancer, and cervical cancer. As a cream it is used for actinic keratosis, basal cell carcinoma, and skin warts.
Carboplatin, sold under the brand name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is used by injection into a vein.
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Oxaliplatin, sold under the brand name Eloxatin among others, is a cancer medication used to treat colorectal cancer. It is given by injection into a vein.
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Adjuvant therapy, also known as adjunct therapy, adjuvant care, or augmentation therapy, is a therapy that is given in addition to the primary or initial therapy to maximize its effectiveness. The surgeries and complex treatment regimens used in cancer therapy have led the term to be used mainly to describe adjuvant cancer treatments. An example of such adjuvant therapy is the additional treatment usually given after surgery where all detectable disease has been removed, but where there remains a statistical risk of relapse due to the presence of undetected disease. If known disease is left behind following surgery, then further treatment is not technically adjuvant.
Tegafur/uracil is a chemotherapy drug combination used in the treatment of cancer, primarily bowel cancer.
The ASAH1 gene encodes in humans the acid ceramidase enzyme.
Fibroblast growth factor 19 is a protein that in humans is encoded by the FGF19 gene. It functions as a hormone, regulating bile acid synthesis, with effects on glucose and lipid metabolism. Reduced synthesis, and blood levels, may be a factor in chronic bile acid diarrhea and in certain metabolic disorders.
Tegafur is a chemotherapeutic prodrug of 5-fluorouracil (5-FU) used in the treatment of cancers. It is a component of the combination drug tegafur/uracil. When metabolised, it becomes 5-FU.
Polysaccharide-K is a protein-bound polysaccharide isolated from the mycelium of Trametes versicolor.
Wafik El-Deiry is an American physician and cancer researcher who is the Associate Dean for Oncologic Sciences at the Warren Alpert Medical School, Brown University, Director of the Cancer Center at Brown University, and the Director of the Joint Program in Cancer Biology at Brown University and its affiliated hospitals. He was previously deputy director of Translational Research at Fox Chase Cancer Center, where he was also co-Leader of the Molecular Therapeutics Program.
Antineoplastic resistance, often used interchangeably with chemotherapy resistance, is the resistance of neoplastic (cancerous) cells, or the ability of cancer cells to survive and grow despite anti-cancer therapies. In some cases, cancers can evolve resistance to multiple drugs, called multiple drug resistance.
FOLFIRINOX is a chemotherapy regimen for treatment of advanced pancreatic cancer. It is made up of the following four drugs:
FOLFOXIRI is a chemotherapy regimen for the treatment of advanced colorectal cancer. The role of FOLFOXIRI in colorectal cancer has been reviewed.
Doxifluridine (5'-deoxy-5-fluorouridine) is a second generation nucleoside analog prodrug developed by Roche and used as a cytostatic agent in chemotherapy in several Asian countries including China and South Korea. Doxifluridine is not FDA-approved for use in the USA. It is currently being evaluated in several clinical trials as a stand-alone or combination therapy treatment.
Metronomic therapy is a new type of chemotherapy in which anti-cancer drugs are administered in a lower dose than the maximum tolerated dose repetitively over a long period to treat cancers with fewer side effects. Metronomic therapy is shown to affect both tumor microenvironment and tumor cells to achieve its therapeutic effects. Metronomic therapy is also cost-effective as a lower dose is used compared to conventional chemotherapy. The use of metronomic therapy has been extensively investigated and can be advantageous in selected group of patients. Yet, more clinical trials are necessary to generalize the method.
BOLD-100, or sodium trans-[tetrachlorobis (1H-indazole)ruthenate(III)], is a ruthenium-based anti-cancer therapeutic in clinical development. As of February 2024, BOLD-100 was being tested in a Phase 1b/2a clinical trial in 117 patients with advanced gastrointestinal cancers in combination with the chemotherapy regimen FOLFOX. BOLD-100 is being developed by Bold Therapeutics Inc.