DB00322 - Floxuridine
| Identification | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Name | Floxuridine | ||||||||||||||||||
| Accession Number | DB00322 (APRD00692) | ||||||||||||||||||
| Type | small molecule | ||||||||||||||||||
| Description | An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection. Floxuridine is available as a sterile, nonpyrogenic, lyophilized powder for reconstitution. When administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract. [PubChem] | ||||||||||||||||||
| Structure |
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| Categories (*) | |||||||||||||||||||
| Molecular Weight | 246.1924 | ||||||||||||||||||
| Groups | approved | ||||||||||||||||||
| Monoisotopic Weight | 246.065199677 | ||||||||||||||||||
| Pharmacology | |||||||||||||||||||
| Indication | For palliative management of gastrointestinal adenocarcinoma metastatic to the liver, when given by continuous regional intra-arterial infusion in carefully selected patients who are considered incurable by surgery or other means. Also for the palliative management of liver cancer (usually administered by hepatic intra-arterial infusion). | ||||||||||||||||||
| Mechanism of action | Floxuridine is rapidly catabolized to 5-fluorouracil, which is the active form of the drug. The primary effect is interference with DNA synthesis and to a lesser extent, inhibition of RNA formation through the drug's incorporation into RNA, thus leading to the production of fraudulent RNA. Fluorouracil also inhibits uracil riboside phophorylase, which prevents the utilization of preformed uracil in RNA synthesis. As well, the monophosphate of floxuridine, 5-fluoro-2'-deoxyuridine-5'-phosphate (FUDR-MP) inhibits the enzyme thymidylate synthetase. This leads to the inhibition of methylation of deoxyuridylic acid to thymidylic acid, thus interfering with DNA synthesis. | ||||||||||||||||||
| Absorption | Not Available | ||||||||||||||||||
| Protein binding | Not Available | ||||||||||||||||||
| Biotransformation | Hepatic. | ||||||||||||||||||
| Route of elimination | The drug is excreted intact and as urea, fluorouracil, a-fluoro-bureidopropionic acid, dihydrofluorouracil, a-fluoro-b-guanidopropionic acid and a-fluoro-b-alanine in the urine; it is also expired as respiratory carbon dioxide. | ||||||||||||||||||
| Toxicity | Oral, rat LD50: 215 mg/kg. Signs of overdose include nausea, vomiting, diarrhea, gastrointestinal ulceration and bleeding, and bone marrow depression (including thrombocytopenia, leukopenia and agranulocytosis). | ||||||||||||||||||
| Affected organisms |
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| Interactions | |||||||||||||||||||
| Drug Interactions |
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| Food Interactions | Not Available | ||||||||||||||||||
Targets
| Thymidylate synthase | |
|---|---|
| Name | Thymidylate synthase |
| Gene Name | TYMS |
| Pharmacological action | yes |
| Actions | Not Available |
| References |
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| DTHybrid score | 0.7329 |
Enzymes
| Thymidine phosphorylase | |
|---|---|
| Name | Thymidine phosphorylase |
| Gene Name | TYMP |
| Actions | substrate |
| References |
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| DTHybrid score | 0.709 |