| Stereochemistry | ABSOLUTE |
| Molecular Formula | C9H10FIN2O5 |
| Molecular Weight | 372.089 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC[C@H]1O[C@H]([C@@H](F)[C@@H]1O)N2C=C(I)C(=O)NC2=O
InChI
InChIKey=IPVFGAYTKQKGBM-BYPJNBLXSA-N
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
| Molecular Formula | C9H10FIN2O5 |
| Molecular Weight | 372.089 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Fialuridine, or 1-(2-deoxy-2-fluoro-1-D-arabinofuranosyl)-5-iodouracil (FIAU) is a thymidine nucleoside analog with activity against various herpesviruses and hepatitis B virus (HBV) in vitro and in vivo. Herpes virus thymidine kinase considered to be a target of FIAU. In a Phase II study, fialuridine induced a severe toxic reaction in chronic hepatitis B patients characterized by hepatic failure, lactic acidosis, pancreatitis, neuropathy, and myopathy. These clinical manifestations led to the hypothesis that the toxicity of FIAU was mediated through mitochondrial dysfunction, possibly as a result of the inhibition of mitochondrial DNA polymerase gamma and/or incorporation of FIAU into mitochondrial DNA.
Originator
Approval Year
Doses
AEs
Sourcing
PubMed
Patents
Sample Use Guides
This phase 2 trial was designed to evaluate the safety and efficacy of a six-month course of fialuridine in 24 patients with chronic hepatitisB. Patients were randomly assigned to receive either 0.10 or 0.25 mg of fialuridine per kilogram of body weight per day given orally in two or three divided doses. In patients with chronic hepatitis B, treatment with fialuridine induced a severe toxic reaction characterized by hepatic failure, lactic acidosis, pancreatitis, neuropathy, and myopathy.
Route of Administration:
Oral
Mitochondria isolated from livers of naive rats were treated in vitro with concentrations of Fialuridine, or 1-(2-deoxy-2-fluoro-1-D-arabinofuranosyl)-5-iodouracil (FIAU) or FIAU triphosphate (FIAU-TP) ranging from 0.1 to 200 microM. A 14 or 32% decrease in mitochondrial DNA synthesis compared to controls was observed when isolated mitochondria were treated with 25 microM FIAU or FIAU-TP, respectively.
