Idoxuridine

Identification

Summary

Idoxuridine is a pyrimidine analog antiviral used for the treatment of viral eye infections, including herpes simplex keratitis.

Generic Name
Idoxuridine
DrugBank Accession Number
DB00249
Background

An analog of deoxyuridine that inhibits viral DNA synthesis. The drug is used as an antiviral agent.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 354.0985
Monoisotopic: 353.971264892
Chemical Formula
C9H11IN2O5
Synonyms
  • (+)-5-Iodo-2'-deoxyuridine
  • 1-(2-Deoxy-beta-D-ribofuranosyl)-5-iodouracil
  • 1-beta-D-2'-Deoxyribofuranosyl-5-iodouracil
  • 1beta-D-2'-Deoxyribofuranosyl-5-iodouracil
  • 2'-Deoxy-5-iodouridine
  • 5-iodo-2'-deoxyuridine
  • 5-Iododeoxyuridine
  • 5-Iodouracil deoxyriboside
  • Idoxuridin
  • Idoxuridina
  • Idoxuridine
  • Idoxuridinum
  • IdU
  • Iododeoxyridine
  • Iodoxuridine
  • Joddeoxiuridin
External IDs
  • ALLERGAN 211
  • ALLERGAN-211
  • NSC-39661
  • SK&F 14287

Pharmacology

Indication

For use in keratoconjunctivitis and keratitis caused by herpes simplex virus.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

In chemical structure idoxuridine closely approximates the configuration of thymidine, one of the four building blocks of DNA (the genetic material of the Herpes virus). As a result, idoxuridine is able to replace thymidine in the enzymatic step of viral replication or "growth". The consequent production of faulty DNA results in a pseudostructure which cannot infect or destroy tissue. In short, by pre-empting a vital building block in the genetic material of the Herpes simplex virus, Herplex-D topical solution destroys the infective and destructive capacity of the viral material. The virus infected cell may only be attacked during the period of active synthesis of DNA. This occurs early in the development of the Herpes simplex lesion, but at different times in different cells. Therefore, ideally, the affected area should remain saturated with the antiviral agent.

Mechanism of action

Idoxuridine acts as an antiviral agent by inhibiting viral replication by substituting itself for thymidine in viral DNA. This in turn inhibits thymidylate phosphorylase and viral DNA polymerases from properly functioning. The effect of Idoxuridine results in the inability of the virus to reproduce or to infect/destroy tissue.

TargetActionsOrganism
ADNA
other
Humans
UThymidine kinase
unknown
HHV-1
Absorption

Systemic absorption is unlikely following ocular administration even when nasolacrimal secretions are swallowed, since vidarabine is rapidly deaminated in the gastrointestinal tract.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Idoxuridine is rapidly inactivated by deaminases or nucleotidases.

Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Hypersensitivity or increased sensitivity of eyes to light. LD50=3080 mg/kg (orally in mice).

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
No interactions found.

Products

Products2
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International/Other Brands
Herpid (Astellas) / Herpidu (Ciba Vision) / Idulea (Elea) / Idustatin (Sanofi) / Keresid (GlaxoSmithKline) / Oftan IDU (Santen) / Virexen (Viñas)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DendridSolution / drops1 mg/1mLOphthalmicALCON LABORATORIES, INC.1963-06-281995-12-31US flag
HerplexSolution / drops.1 %OphthalmicAllergan1963-12-312011-08-04Canada flag
Herplex DLiquid.1 %TopicalAllergan1967-12-312011-08-04Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Sandoz IdoxuridineLiquid0.1 %TopicalSandoz Canada Incorporated1999-02-152019-08-01Canada flag

Categories

ATC Codes
D06BB01 — IdoxuridineJ05AB02 — IdoxuridineS01AD01 — Idoxuridine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleosides. These are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at position 2.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Pyrimidine nucleosides
Sub Class
Pyrimidine 2'-deoxyribonucleosides
Direct Parent
Pyrimidine 2'-deoxyribonucleosides
Alternative Parents
Pyrimidones / Halopyrimidines / Hydroxypyrimidines / Aryl iodides / Hydropyrimidines / Tetrahydrofurans / Heteroaromatic compounds / Secondary alcohols / Oxacyclic compounds / Azacyclic compounds
show 6 more
Substituents
Alcohol / Aromatic heteromonocyclic compound / Aryl halide / Aryl iodide / Azacycle / Halopyrimidine / Heteroaromatic compound / Hydrocarbon derivative / Hydropyrimidine / Hydroxypyrimidine
show 16 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organoiodine compound, pyrimidine 2'-deoxyribonucleoside (CHEBI:147675)
Affected organisms
  • Herpes simplex virus

Chemical Identifiers

UNII
LGP81V5245
CAS number
54-42-2
InChI Key
XQFRJNBWHJMXHO-RRKCRQDMSA-N
InChI
InChI=1S/C9H11IN2O5/c10-4-2-12(9(16)11-8(4)15)7-1-5(14)6(3-13)17-7/h2,5-7,13-14H,1,3H2,(H,11,15,16)/t5-,6+,7+/m0/s1
IUPAC Name
1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodo-1,2,3,4-tetrahydropyrimidine-2,4-dione
SMILES
OC[C@H]1O[C@H](C[C@@H]1O)N1C=C(I)C(=O)NC1=O

References

Synthesis Reference

British Patent 1,024,156.

General References
  1. Seth AK, Misra A, Umrigar D: Topical liposomal gel of idoxuridine for the treatment of herpes simplex: pharmaceutical and clinical implications. Pharm Dev Technol. 2004 Aug;9(3):277-89. [Article]
  2. Otto SE: Radiopharmaceuticals (Strontium 89) and radiosensitizers (idoxuridine). J Intraven Nurs. 1998 Nov-Dec;21(6):335-7. [Article]
  3. Fauth E, Zankl H: Comparison of spontaneous and idoxuridine-induced micronuclei by chromosome painting. Mutat Res. 1999 Apr 6;440(2):147-56. [Article]
Human Metabolome Database
HMDB0014394
KEGG Drug
D00342
PubChem Compound
5905
PubChem Substance
46507573
ChemSpider
5694
BindingDB
50370388
RxNav
5653
ChEBI
147675
ChEMBL
CHEMBL788
ZINC
ZINC000003834173
Therapeutic Targets Database
DAP000997
PharmGKB
PA164781019
PDBe Ligand
ID2
Drugs.com
Drugs.com Drug Page
Wikipedia
Idoxuridine
PDB Entries
1ki7
MSDS
Download (73.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Unknown StatusTreatmentLeukemias1

Pharmacoeconomics

Manufacturers
  • Glaxosmithkline
  • Alcon laboratories inc
  • Allergan pharmaceutical
Packagers
  • Medisca Inc.
Dosage Forms
FormRouteStrength
Solution / dropsOphthalmic
Solution / dropsOphthalmic1 mg/1mL
SolutionTopical5 g
Solution / dropsOphthalmic.1 %
LiquidTopical.1 %
OintmentOphthalmic
CreamTopical
SolutionTopical
LiquidTopical0.1 %
Prices
Unit descriptionCostUnit
Idoxuridine powder273.88USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)193British Patent 1,024,156.
water solubility2000 mg/L (at 25 °C)MERCK INDEX (1996)
logP-0.96NARURKAR,MM & MITRA,AK (1988)
Predicted Properties
PropertyValueSource
Water Solubility23.4 mg/mLALOGPS
logP-0.7ALOGPS
logP-0.53ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)8.46ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area99.1 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity64.4 m3·mol-1ChemAxon
Polarizability26.17 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.8129
Blood Brain Barrier+0.6502
Caco-2 permeable-0.8707
P-glycoprotein substrateNon-substrate0.7139
P-glycoprotein inhibitor INon-inhibitor0.8735
P-glycoprotein inhibitor IINon-inhibitor0.8719
Renal organic cation transporterNon-inhibitor0.8943
CYP450 2C9 substrateNon-substrate0.7834
CYP450 2D6 substrateNon-substrate0.8656
CYP450 3A4 substrateNon-substrate0.5445
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9108
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9093
CYP450 3A4 inhibitorNon-inhibitor0.8932
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8505
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.7699
BiodegradationNot ready biodegradable0.9542
Rat acute toxicity2.0879 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9356
hERG inhibition (predictor II)Non-inhibitor0.8113
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Other
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
References
  1. Komissarova NV, Tiunova AA, Anokhin KV: Selective impairments to memory consolidation in chicks produced by 5'-iodo-2'-deoxyuridine. Neurosci Behav Physiol. 2010 Feb;40(2):215-23. doi: 10.1007/s11055-009-9237-0. Epub 2009 Dec 22. [Article]
  2. Komissarova NV, Tiunova AA, Anokhin KV: [Selective disruption of memory consolidation in chicks produced by 5'-iodo-2'-deoxyuridine]. Zh Vyssh Nerv Deiat Im I P Pavlova. 2008 Nov-Dec;58(6):700-10. [Article]
Kind
Protein
Organism
HHV-1
Pharmacological action
Unknown
Actions
Unknown
General Function
Thymidine kinase activity
Specific Function
In latent infection, may allow the virus to be reactivated and to grow in cells lacking a high concentration of phosphorylated nucleic acid precursors, such as nerve cells that do not replicate the...
Gene Name
TK
Uniprot ID
Q9QNF7
Uniprot Name
Thymidine kinase
Molecular Weight
40896.475 Da
References
  1. Wild K, Bohner T, Folkers G, Schulz GE: The structures of thymidine kinase from herpes simplex virus type 1 in complex with substrates and a substrate analogue. Protein Sci. 1997 Oct;6(10):2097-106. [Article]

Drug created on June 13, 2005 13:24 / Updated on September 28, 2021 07:54