| Iupac Name: | 1-[(2''R'',3''R'',4''S'',5''R'')-3,4-Dihydroxy-5-methyloxolan-2-yl]-5-fluoropyrimidine-2,4-dione |
| Width: | 150px |
| Cas Number: | 3094-09-5 |
| Unii: | V1JK16Y2JP |
| Pubchem: | 18343 |
| Chemspiderid: | 17322 |
| Synonyms: | Doxyfluridine; doxifluridine; 5'-deoxy-5-fluorouridine; 5'-deoxy-5'-fluorouridine; 5'-fluoro-5'-deoxyuridine; 5'-dFUrd; 5'-DFUR; Furtulon; Ro 21-9738 |
| C: | 9 |
| H: | 11 |
| F: | 1 |
| N: | 2 |
| O: | 5 |
| Stdinchi: | 1S/C9H11FN2O5/c1-3-5(13)6(14)8(17-3)12-2-4(10)7(15)11-9(12)16/h2-3,5-6,8,13-14H,1H3,(H,11,15,16)/t3-,5-,6-,8-/m1/s1 |
| Stdinchikey: | ZWAOHEXOSAUJHY-ZIYNGMLESA-N |
| Smiles: | C[C@@H]1[C@H]([C@H]([C@@H](O1)N2C=C(C(=O)NC2=O)F)O)O |
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.[1] 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.
5-Fluorouracil (5-FU), the nucleobase of doxifluridine, is currently an FDA-approved antimetabolite.[2] 5-FU is normally administered intravenously to prevent its degradation by dihydropyrimidine dehydrogenase in the gut wall. Doxifluridine is a fluoropyrimidine derivative of 5-FU, thus a second-generation nucleoside prodrug. Doxifluridine was designed to improve oral bioavailability in order to avoid dihydropyrimidine dehydrogenase degradation in the digestive system.[3]
Within a cell, pyrimidine nucleoside phosphorylase or thymidine phosphorylase can metabolize doxifluridine into 5-FU.[4] [5] It is also a metabolite of capecitabine.[4] High levels of pyrimidine-nucleoside phosphorylase and thymidine phosphorylase are expressed in esophageal, breast, cervical, pancreatic, and hepatic cancers.[6] [7] Liberation of 5-FU is the active metabolite and leads to inhibition of DNA synthesis and cell death.
High thymidine phosphorylase expression is also found in the human intestinal tract, resulting in dose-limiting toxicity (diarrhea) in some individuals.[8]
The most frequent adverse effects for doxifluridine were neurotoxicity and mucositis.
Doxifluridine is sold under many brand names:[9]
| Brand name | Company | Country |
|---|---|---|
| Didox[10] | Shin Poong Pharm. Co., Ltd. | South Korea |
| Doxyfluridine | Kwang Dong | |
| Doxifluridine cap | Myungmoon Pharma Co. Ltd. | |
| Ai Feng | Hengrui | China and Japan |
| Doxifluridine | XinShiDai Pharmaceutical | |
| Furtulon | Roche, Chugai | |
| Ke Fu | Zhaohui | |
| Ke Tuo | Southwest | |
| Qi Nuo Bi Tong | Wanjie High-Tech | |
| Shu Qi | Team | |
| Tan Nuo | Xinchang Medicine & Chemical Co Ltd | |
| Yi Di An | Pacific |