Details
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 |
|
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/218006
Curator's Comment: reference retrieved from https://www.ncbi.nlm.nih.gov/pubmed/6239591
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2732 |
0.015 µM [Ki] | ||
Target ID: CHEMBL1795127 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3015003 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Doses
Dose | Population | Adverse events |
---|---|---|
0.25 mg/kg 2 times / day multiple, oral (max,total daily dose) Highest studied dose Dose: 0.25 mg/kg, 2 times / day Route: oral Route: multiple Dose: 0.25 mg/kg, 2 times / day Sources: Page: p.1100 |
unhealthy, ADULT n = 15 Health Status: unhealthy Condition: chronic hepatitis B Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: Page: p.1100 |
Disc. AE: Liver failure, Pancreatitis... Other AEs: Neuropathy... AEs leading to discontinuation/dose reduction: Liver failure (grade 5, 33.3%) Other AEs:Pancreatitis (grade 5, 33.3%) Lactic acidosis (grade 5, 33.3%) Pancreatitis (46.7%) Lactic acidosis (46.7%) Liver failure (46.7%) Neuropathy (grade 1-2, 33.3%) Sources: Page: p.1100 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Lactic acidosis | 46.7% Disc. AE |
0.25 mg/kg 2 times / day multiple, oral (max,total daily dose) Highest studied dose Dose: 0.25 mg/kg, 2 times / day Route: oral Route: multiple Dose: 0.25 mg/kg, 2 times / day Sources: Page: p.1100 |
unhealthy, ADULT n = 15 Health Status: unhealthy Condition: chronic hepatitis B Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: Page: p.1100 |
Liver failure | 46.7% Disc. AE |
0.25 mg/kg 2 times / day multiple, oral (max,total daily dose) Highest studied dose Dose: 0.25 mg/kg, 2 times / day Route: oral Route: multiple Dose: 0.25 mg/kg, 2 times / day Sources: Page: p.1100 |
unhealthy, ADULT n = 15 Health Status: unhealthy Condition: chronic hepatitis B Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: Page: p.1100 |
Pancreatitis | 46.7% Disc. AE |
0.25 mg/kg 2 times / day multiple, oral (max,total daily dose) Highest studied dose Dose: 0.25 mg/kg, 2 times / day Route: oral Route: multiple Dose: 0.25 mg/kg, 2 times / day Sources: Page: p.1100 |
unhealthy, ADULT n = 15 Health Status: unhealthy Condition: chronic hepatitis B Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: Page: p.1100 |
Neuropathy | grade 1-2, 33.3% | 0.25 mg/kg 2 times / day multiple, oral (max,total daily dose) Highest studied dose Dose: 0.25 mg/kg, 2 times / day Route: oral Route: multiple Dose: 0.25 mg/kg, 2 times / day Sources: Page: p.1100 |
unhealthy, ADULT n = 15 Health Status: unhealthy Condition: chronic hepatitis B Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: Page: p.1100 |
Lactic acidosis | grade 5, 33.3% Disc. AE |
0.25 mg/kg 2 times / day multiple, oral (max,total daily dose) Highest studied dose Dose: 0.25 mg/kg, 2 times / day Route: oral Route: multiple Dose: 0.25 mg/kg, 2 times / day Sources: Page: p.1100 |
unhealthy, ADULT n = 15 Health Status: unhealthy Condition: chronic hepatitis B Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: Page: p.1100 |
Liver failure | grade 5, 33.3% Disc. AE |
0.25 mg/kg 2 times / day multiple, oral (max,total daily dose) Highest studied dose Dose: 0.25 mg/kg, 2 times / day Route: oral Route: multiple Dose: 0.25 mg/kg, 2 times / day Sources: Page: p.1100 |
unhealthy, ADULT n = 15 Health Status: unhealthy Condition: chronic hepatitis B Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: Page: p.1100 |
Pancreatitis | grade 5, 33.3% Disc. AE |
0.25 mg/kg 2 times / day multiple, oral (max,total daily dose) Highest studied dose Dose: 0.25 mg/kg, 2 times / day Route: oral Route: multiple Dose: 0.25 mg/kg, 2 times / day Sources: Page: p.1100 |
unhealthy, ADULT n = 15 Health Status: unhealthy Condition: chronic hepatitis B Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: Page: p.1100 |
PubMed
Title | Date | PubMed |
---|---|---|
Differential activity of potential antiviral nucleoside analogs on herpes simplex virus-induced and human cellular thymidine kinases. | 1981 Sep |
|
The in vitro anti-hepatitis B virus activity of FIAU [1-(2'-deoxy-2'-fluoro-1-beta-D-arabinofuranosyl-5-iodo)uracil] is selective, reversible, and determined, at least in part, by the host cell. | 1994 Jan |
|
In vitro activity of potential anti-poxvirus agents. | 2003 Jan |
|
Biodistribution, cellular uptake and DNA-incorporation of the 2'-fluoro stabilized 5-iodo-2'-deoxyuridine analog 5-iodo-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil (FIAU). | 2008 Sep |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7565947
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9107387
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.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 14:24:57 UTC 2023
by
admin
on
Sat Dec 16 14:24:57 UTC 2023
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Record UNII |
53T7IN77LC
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Record Status |
Validated (UNII)
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Record Version |
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-
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
67892
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NCI_THESAURUS |
C1557
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NCI_THESAURUS |
C281
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NCI_THESAURUS |
C29575
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678514
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CC-21
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m5368
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53T7IN77LC
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100000080966
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DTXSID701028030
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69123-98-4
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SUB07622MIG
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C73197
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50313
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DB15427
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CHEMBL271475
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FIALURIDINE
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7051
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C043457
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