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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
Structure of FIALURIDINE

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

HIDE SMILES / InChI

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

Curator's Comment: reference retrieved from https://www.ncbi.nlm.nih.gov/pubmed/6239591

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse 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%)
Pancreatitis (grade 5, 33.3%)
Lactic acidosis (grade 5, 33.3%)
Pancreatitis (46.7%)
Lactic acidosis (46.7%)
Liver failure (46.7%)
Other AEs:
Neuropathy (grade 1-2, 33.3%)
Sources: Page: p.1100
AEs

AEs

AESignificanceDosePopulation
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
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 >1000 uM]
yes [Ki 0.015 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Nucleosides. 110. Synthesis and antiherpes virus activity of some 2'-fluoro-2'-deoxyarabinofuranosylpyrimidine nucleosides.
1979 Jan
Differential activity of potential antiviral nucleoside analogs on herpes simplex virus-induced and human cellular thymidine kinases.
1981 Sep
Efficacy and selectivity of some nucleoside analogs as anti-human cytomegalovirus agents.
1983 Oct
Activities of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine and its metabolites against herpes simplex virus types 1 and 2 in cell culture and in mice infected intracerebrally with herpes simplex virus type 2.
1986 Jan
2'-Fluorinated arabinonucleosides of 5-(2-haloalkyl)uracil: synthesis and antiviral activity.
1987 Jul
Multiple nuclear dots antinuclear antibodies are not specific for primary biliary cirrhosis.
1992 Jul
Use of a standardized cell culture assay to assess activities of nucleoside analogs against hepatitis B virus replication.
1992 Jul 1
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
Falsely low calcium measurements after high volume plasma exchange in a patient with liver failure.
1994 Sep
Structure-activity relationship of the affinity of 5-substituted uracil nucleoside analogues for varicella-zoster virus thymidine kinase and their activity against varicella-zoster virus.
1997 Aug
Identification of BMS-200475 as a potent and selective inhibitor of hepatitis B virus.
1997 Jul
Anti-herpesvirus activity profile of 4'-thioarabinofuranosyl purine and uracil nucleosides and activity of 1-beta-D-2'-fluoro-4'-thioarabinofuranosyl guanine and 2,6-diaminopurine against clinical isolates of human cytomegalovirus.
1998 Aug
Enhanced inhibition of orthopoxvirus replication in vitro by alkoxyalkyl esters of cidofovir and cyclic cidofovir.
2002 Apr
In vitro activity of potential anti-poxvirus agents.
2003 Jan
Specific genetic modifications of domestic animals by gene targeting and animal cloning.
2003 Nov 13
Development of radioiodinated nucleoside analogs for imaging tissue proliferation: comparisons of six 5-iodonucleosides.
2003 Oct
Anti-cowpox virus activities of certain adenosine analogs, arabinofuranosyl nucleosides, and 2'-fluoro-arabinofuranosyl nucleosides.
2004
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
Facilitated mitochondrial import of antiviral and anticancer nucleoside drugs by human equilibrative nucleoside transporter-3.
2009 Apr
Myopathy and neuropathy associated with nucleos(t)ide analog therapy for hepatitis B.
2009 Oct
Effects of structural differences between radioiodine-labeled 1-(2'-fluoro-2'-deoxy-D-arabinofuranosyl)-5-iodouracil (FIAU) and 1-(2'-fluoro-2'-deoxy-d-ribofuranosyl)-5-iodouracil (FIRU) on HSV1-TK reporter gene imaging.
2010 Jun
A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans.
2014 Jan
Patents

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
In Vitro Use Guide
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 Thu Jul 06 20:00:29 UTC 2023
Edited
by admin
on Thu Jul 06 20:00:29 UTC 2023
Record UNII
53T7IN77LC
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FIALURIDINE
INN   MART.   MI   USAN  
USAN   INN  
Official Name English
FIALURIDINE [USAN]
Common Name English
1-(2-DEOXY-2-FLUORO-.BETA.-D-ARABINOFURANOSYL)-5-IODOURACIL
Common Name English
FIALURIDINE [MART.]
Common Name English
FIALURIDINE [MI]
Common Name English
NSC-678514
Code English
fialuridine [INN]
Common Name English
2,4(1H,3H)-PYRIMIDINEDIONE, 1-(2-DEOXY-2-FLUORO-.BETA.-D-ARABINOFURANOSYL)-5-IODO-
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 67892
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
NCI_THESAURUS C1557
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
NCI_THESAURUS C281
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
NCI_THESAURUS C29575
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
Code System Code Type Description
NSC
678514
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
PRIMARY
USAN
CC-21
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
PRIMARY
MERCK INDEX
M5368
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
PRIMARY Merck Index
FDA UNII
53T7IN77LC
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
PRIMARY
SMS_ID
100000080966
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
PRIMARY
EPA CompTox
DTXSID701028030
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
PRIMARY
CAS
69123-98-4
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
PRIMARY
EVMPD
SUB07622MIG
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
PRIMARY
NCI_THESAURUS
C73197
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
PRIMARY
PUBCHEM
50313
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
PRIMARY
DRUG BANK
DB15427
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
PRIMARY
ChEMBL
CHEMBL271475
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
PRIMARY
WIKIPEDIA
FIALURIDINE
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
PRIMARY
INN
7051
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
PRIMARY
MESH
C043457
Created by admin on Thu Jul 06 20:00:29 UTC 2023 , Edited by admin on Thu Jul 06 20:00:29 UTC 2023
PRIMARY
Related Record Type Details
ACTIVE MOIETY