Identification

Name
Vidarabine
Accession Number
DB00194
Description

A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the vaccinia VIRUS and varicella zoster virus.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 267.2413
Monoisotopic: 267.096753929
Chemical Formula
C10H13N5O4
Synonyms
  • 9-beta-D-arabinofuranosyl-9H-purin-6-amine
  • 9-beta-D-arabinofuranosyl-adenine
  • 9-beta-D-Arabinofuranosyladenine
  • 9-β-D-arabinofuranosyl-9H-purin-6-amine
  • 9-β-D-arabinofuranosyladenine
  • Spongoadenosine
  • Vidarabine
  • Vidarabinum

Pharmacology

Indication

For treatment of chickenpox - varicella, herpes zoster and herpes simplex

Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Vidarabine is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV). The inhibitory activity of Vidarabine is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts Vidarabine into Vidarabine monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In vitro, Vidarabine triphosphate stops the DNA replication of herpes virus by being incorporated into the DNA strand and preventing the formation of phosphodiester bridges between bases. This ultimately leads to destabilization of the viral DNA strands.

Mechanism of action

Vidarabine stops replication of herpes viral DNA in 2 ways: 1) competitive inhibition of viral DNA polymerase, and consequently 2) incorporation into and termination of the growing viral DNA chain. Vidarabine is sequentially phosphorylated by kinases to the triphosphate ara-ATP, which is the active form of vidarabine that acts as both an inhibitor and a substrate of viral DNA polymerase. By acting as a substrate for viral DNA polymerase, ara-ATP competitively inhibits dATP leading to the formation of ‘faulty’ DNA. Ara-ATP can also be incorporated into the DNA strand to replace many of the adenosine bases, resulting in the disruption of DNA synthesis.

TargetActionsOrganism
ADNA polymerase catalytic subunit
inhibitor
HHV-1
AThymidine kinase
inducer
AThymidine kinase
inducer
HHV-1
Absorption

Systemetic absorption of vidarabine should not be expected to occur following ocular administration and swallowing lacrimal secretions.

Volume of distribution
Not Available
Protein binding

24-38%

Metabolism

In laboratory animals, vidarabine is rapidly deaminated in the gastrointestinal tract to Ara-Hx.

Route of elimination
Not Available
Half-life
Not Available
Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Acute massive overdosage by oral ingestion of the ophthalmic ointment has not occurred. However, the rapid deamination to arabinosylhypoxanthine should preclude any difficulty. The oral LD50 for vidarabine is greater than 5020 mg/kg in mice and rats. No untoward effects should result from ingestion of the entire contents of the tube. Overdosage by ocular instillation is unlikely because any excess should be quickly expelled from the conjunctival sac.

Affected organisms
  • Human Herpes Virus
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.
DrugInteraction
AllopurinolThe metabolism of Allopurinol can be decreased when combined with Vidarabine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
Not Available

Products

International/Other Brands
Arasena-A
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Vira-AOintment30 mg/1gTopicalMonarch Pharmaceuticals, Inc.1976-11-262001-12-07Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more

Categories

ATC Codes
J05AB03 — VidarabineS01AD06 — Vidarabine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as purine nucleosides. These are compounds comprising a purine base attached to a ribosyl or deoxyribosyl moiety.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Purine nucleosides
Sub Class
Not Available
Direct Parent
Purine nucleosides
Alternative Parents
Glycosylamines / Pentoses / 6-aminopurines / Aminopyrimidines and derivatives / N-substituted imidazoles / Imidolactams / Tetrahydrofurans / Heteroaromatic compounds / Secondary alcohols / Oxacyclic compounds
show 5 more
Substituents
6-aminopurine / Alcohol / Amine / Aminopyrimidine / Aromatic heteropolycyclic compound / Azacycle / Azole / Glycosyl compound / Heteroaromatic compound / Hydrocarbon derivative
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
purine nucleoside, beta-D-arabinoside (CHEBI:45327)

Chemical Identifiers

UNII
3XQD2MEW34
CAS number
24356-66-9
InChI Key
OIRDTQYFTABQOQ-UHTZMRCNSA-N
InChI
InChI=1S/C10H13N5O4/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(18)6(17)4(1-16)19-10/h2-4,6-7,10,16-18H,1H2,(H2,11,12,13)/t4-,6-,7+,10-/m1/s1
IUPAC Name
(2R,3S,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
SMILES
NC1=NC=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O

References

General References
Not Available
Human Metabolome Database
HMDB0014340
KEGG Drug
D00406
KEGG Compound
C07195
PubChem Compound
21704
PubChem Substance
46506630
ChemSpider
20400
BindingDB
50144936
RxNav
11194
ChEBI
45327
ChEMBL
CHEMBL1090
ZINC
ZINC000000970363
Therapeutic Targets Database
DAP000642
PharmGKB
PA451876
PDBe Ligand
RAB
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Vidarabine
PDB Entries
1pw7 / 3glq
MSDS
Download (73.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentHerpes Simplex / Human Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
  • Parkedale pharmaceuticals inc
Packagers
  • Medisca Inc.
  • Professional Co.
Dosage Forms
FormRouteStrength
OintmentTopical30 mg/1g
Prices
Unit descriptionCostUnit
Vidarabine monohydrate powder687.0USD g
Vidarabine powder366.59USD 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
logP-2.115Not Available
Predicted Properties
PropertyValueSource
Water Solubility14.0 mg/mLALOGPS
logP-1.2ALOGPS
logP-2.1ChemAxon
logS-1.3ALOGPS
pKa (Strongest Acidic)12.45ChemAxon
pKa (Strongest Basic)4.99ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area139.54 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity63.2 m3·mol-1ChemAxon
Polarizability24.49 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9227
Blood Brain Barrier+0.9383
Caco-2 permeable-0.8957
P-glycoprotein substrateNon-substrate0.7026
P-glycoprotein inhibitor INon-inhibitor0.966
P-glycoprotein inhibitor IINon-inhibitor0.9533
Renal organic cation transporterNon-inhibitor0.9444
CYP450 2C9 substrateNon-substrate0.8639
CYP450 2D6 substrateNon-substrate0.8349
CYP450 3A4 substrateNon-substrate0.5866
CYP450 1A2 substrateNon-inhibitor0.9667
CYP450 2C9 inhibitorNon-inhibitor0.9595
CYP450 2D6 inhibitorNon-inhibitor0.977
CYP450 2C19 inhibitorNon-inhibitor0.9514
CYP450 3A4 inhibitorNon-inhibitor0.962
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9701
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9182
BiodegradationNot ready biodegradable0.9738
Rat acute toxicity1.9715 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.989
hERG inhibition (predictor II)Non-inhibitor0.9102
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-2910000000-e18a8d00eb0e73aa6dec

Targets

Kind
Protein
Organism
HHV-1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Rna-dna hybrid ribonuclease activity
Specific Function
Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding pro...
Gene Name
Not Available
Uniprot ID
P04293
Uniprot Name
DNA polymerase catalytic subunit
Molecular Weight
136419.66 Da
References
  1. Suzuki M, Okuda T, Shiraki K: Synergistic antiviral activity of acyclovir and vidarabine against herpes simplex virus types 1 and 2 and varicella-zoster virus. Antiviral Res. 2006 Nov;72(2):157-61. Epub 2006 May 30. [PubMed:16797734]
  2. Sagar S, Kaur M, Minneman KP: Antiviral lead compounds from marine sponges. Mar Drugs. 2010 Oct 11;8(10):2619-38. doi: 10.3390/md8102619. [PubMed:21116410]
Kind
Protein
Organism
Not Available
Pharmacological action
Yes
Actions
Inducer
General Function
Catalyzes the transfer of the gamma-phospho group of ATP to thymidine to generate dTMP in the salvage pathway of pyrimidine synthesis. The dTMP serves as a substrate for DNA polymerase during viral DNA replication. Allows the virus to be reactivated and to grow in non-proliferative cells lacking a high concentration of phosphorylated nucleic acid precursors.
Specific Function
Atp binding
Gene Name
TK
Uniprot ID
P09250
Uniprot Name
Thymidine kinase
Molecular Weight
37816.49 Da
References
  1. Suzuki M, Okuda T, Shiraki K: Synergistic antiviral activity of acyclovir and vidarabine against herpes simplex virus types 1 and 2 and varicella-zoster virus. Antiviral Res. 2006 Nov;72(2):157-61. Epub 2006 May 30. [PubMed:16797734]
  2. Henrot A: [Mother-infant and indirect transmission of HSV infection: treatment and prevention]. Ann Dermatol Venereol. 2002 Apr;129(4 Pt 2):533-49. [PubMed:12122323]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
HHV-1
Pharmacological action
Yes
Actions
Inducer
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. Suzuki M, Okuda T, Shiraki K: Synergistic antiviral activity of acyclovir and vidarabine against herpes simplex virus types 1 and 2 and varicella-zoster virus. Antiviral Res. 2006 Nov;72(2):157-61. Epub 2006 May 30. [PubMed:16797734]
  2. Henrot A: [Mother-infant and indirect transmission of HSV infection: treatment and prevention]. Ann Dermatol Venereol. 2002 Apr;129(4 Pt 2):533-49. [PubMed:12122323]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Zinc ion binding
Specific Function
Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine. Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, an...
Gene Name
ADA
Uniprot ID
P00813
Uniprot Name
Adenosine deaminase
Molecular Weight
40764.13 Da
References
  1. Agarwal RP, Blatt J, Miser J, Sallan S, Lipton JM, Reaman GH, Holcenberg J, Poplack DG: Clinical pharmacology of 9-beta-D-arabinofuranosyladenine in combination with 2'-deoxycoformycin. Cancer Res. 1982 Sep;42(9):3884-6. [PubMed:6980706]
  2. Balzarini J, De Clercq E: The antiviral activity of 9-beta-D-arabinofuranosyladenine is enhanced by the 2',3'-dideoxyriboside, the 2',3'-didehydro-2',3'-dideoxyriboside and the 3'-azido-2',3'-dideoxyriboside of 2,6-diaminopurine. Biochem Biophys Res Commun. 1989 Feb 28;159(1):61-7. [PubMed:2538128]
  3. Cristalli G, Franchetti P, Grifantini M, Vittori S, Lupidi G, Riva F, Bordoni T, Geroni C, Verini MA: Adenosine deaminase inhibitors. Synthesis and biological activity of deaza analogues of erythro-9-(2-hydroxy-3-nonyl)adenine. J Med Chem. 1988 Feb;31(2):390-3. [PubMed:3339608]

Drug created on June 13, 2005 07:24 / Updated on June 12, 2020 10:51

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates