Fialuridine

Fialuridine, or 1-(2-deoxy-2-fluoro-1-D-arabinofuranosyl)-5-iodouracil (FIAU), is a nucleoside analogue that was investigated as a potential therapy for hepatitis B virus infection. In a 1993 clinical study at the NIH, unexpected toxicity led to the death of 5 out of 15 patients from liver failure alongside lactic acidosis; two further participants required liver transplantation. It is suspected that the toxicity of fialuridine was a result of mitochondrial damage caused by the incorporation of fialuridine into mitochondrial DNA via its 3'-hydroxyl moiety, leading to impaired DNA synthesis. This toxicity was unusual in that it was not predicted by animal studies.[1][2][3]

Fialuridine
Skeletal formula
Ball-and-stick model
Clinical data
Other names2′-Fluoro-5-iodouracil
ATC code
  • none
Identifiers
  • 1-[(2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)- 2-tetrahydrofuranyl]-5-iodopyrimidine-2,4-dione
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
NIAID ChemDB
Chemical and physical data
FormulaC9H10FIN2O5
Molar mass372.091 g·mol−1
3D model (JSmol)
  • c1c(c(=O)[nH]c(=O)n1[C@H]2[C@H]([C@@H]([C@H](O2)CO)O)F)I
  • InChI=1S/C9H10FIN2O5/c10-5-6(15)4(2-14)18-8(5)13-1-3(11)7(16)12-9(13)17/h1,4-6,8,14-15H,2H2,(H,12,16,17)/t4-,5+,6-,8-/m1/s1 ☒N
  • Key:IPVFGAYTKQKGBM-BYPJNBLXSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

References
  1. Tujios S, Fontana RJ (April 2011). "Mechanisms of drug-induced liver injury: from bedside to bench". Nature Reviews. Gastroenterology & Hepatology. 8 (4): 202–11. doi:10.1038/nrgastro.2011.22. PMID 21386809. S2CID 1329655.
  2. McKenzie R, Fried MW, Sallie R, Conjeevaram H, Di Bisceglie AM, Park Y, et al. (October 1995). "Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B". The New England Journal of Medicine. 333 (17): 1099–105. doi:10.1056/NEJM199510263331702. PMID 7565947.
  3. Thomson L (1 March 1994). "The Cure that Killed". Discover Magazine. Retrieved 2 November 2013.
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