Doxifluridine

Doxifluridine

Clinical data
Other names	Doxyfluridine; doxifluridine; 5'-deoxy-5-fluorouridine; 5'-deoxy-5'-fluorouridine; 5'-fluoro-5'-deoxyuridine; 5'-dFUrd; 5'-DFUR; Furtulon; Ro 21-9738
Identifiers
IUPAC name 1-[(2R,3R,4S,5R)-3,4-Dihydroxy-5-methyloxolan-2-yl]-5-fluoropyrimidine-2,4-dione
CAS Number	3094-09-5 Y
PubChem CID	18343
ChemSpider	17322
UNII	V1JK16Y2JP
Chemical and physical data
Formula	C9H11FN2O5
Molar mass	246.194 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@@H]1[C@H]([C@H]([C@@H](O1)N2C=C(C(=O)NC2=O)F)O)O
InChI InChI=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 Key:ZWAOHEXOSAUJHY-ZIYNGMLESA-N

Doxifluridine 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 (5´-deoxy-5-fluorouridine) 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.^{[citation needed]}

Doxifluridine is sold under many brand names:^[9]

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