Fialuridine, or 1-(2-deoxy-2-fluoro-1-D-arabinofuranosyl)-5-iodouracil (FIAU), is a

nucleoside analogue Nucleoside analogues are structural analogues of a nucleoside, which normally contain a nucleobase and a sugar. Nucleotide analogues are analogues of a nucleotide, which normally has one to three phosphates linked to a nucleoside. Both types ...

that was investigated as a potential therapy for

hepatitis B virus Hepatitis B virus (HBV) is a partially double-stranded DNA virus, a species of the genus '' Orthohepadnavirus'' and a member of the '' Hepadnaviridae'' family of viruses. This virus causes the disease hepatitis B. Classification Hepatitis B ...

infection. In a 1993 clinical study at the

NIH The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...

, unexpected toxicity led to the death of 5 out of 15 patients from

liver failure Liver failure is the inability of the liver to perform its normal synthetic and metabolic functions as part of normal physiology. Two forms are recognised, acute and chronic (cirrhosis). Recently, a third form of liver failure known as acute- ...

alongside

lactic acidosis Lactic acidosis refers to the process leading to the production of lactate by anaerobic metabolism. It increases hydrogen ion concentration tending to the state of acidemia or low pH. The result can be detected with high levels of lactate and lo ...

; two further participants required

liver transplantation Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, al ...

. It is suspected that the toxicity of fialuridine was a result of mitochondrial damage caused by the incorporation of fialuridine into

mitochondrial DNA Mitochondrial DNA (mtDNA and mDNA) is the DNA located in the mitochondrion, mitochondria organelles in a eukaryotic cell that converts chemical energy from food into adenosine triphosphate (ATP). Mitochondrial DNA is a small portion of the D ...

via its 3'-hydroxyl moiety, leading to impaired DNA synthesis. This toxicity was unusual in that it was not predicted by animal studies.

References

Antiviral drugs Nucleosides Organofluorides Organoiodides withdrawn drugs Tetrahydrofurans Diols Pyrimidinediones Arabinosides Clinical trial disasters Hydroxymethyl compounds {{antiinfective-drug-stub