You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameVidarabine
Accession NumberDB00194  (APRD00333, EXPT02753)
TypeSmall Molecule
GroupsApproved
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. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
2-(6-AMINO-purin-9-yl)-5-hydroxymethyl-tetrahydro-furan-3,4-diolNot AvailableNot Available
9-beta-D-Arabinofuranosyl-9H-purin-6-amineNot AvailableNot Available
9-beta-D-arabinofuranosyl-adenineNot AvailableNot Available
9-beta-D-ArabinofuranosyladenineNot AvailableNot Available
9-β-D-arabinofuranosyl-9H-purin-6-amineNot AvailableNot Available
9-β-D-arabinofuranosyladenineNot AvailableNot Available
SpongoadenosineNot AvailableNot Available
VidarabineNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
Arasena-ANot Available
Vira-ANot Available
Brand mixturesNot Available
Categories
CAS number24356-66-9
WeightAverage: 267.2413
Monoisotopic: 267.096753929
Chemical FormulaC10H13N5O4
InChI KeyOIRDTQYFTABQOQ-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganooxygen Compounds
ClassCarbohydrates and Carbohydrate Conjugates
SubclassGlycosyl Compounds
Direct parentPurine Nucleosides and Analogues
Alternative parentsPentoses; Purines and Purine Derivatives; Aminopyrimidines and Derivatives; N-substituted Imidazoles; Primary Aromatic Amines; Tetrahydrofurans; Oxolanes; Secondary Alcohols; 1,2-Diols; Ethers; Primary Alcohols; Polyamines
Substituentspentose monosaccharide; imidazopyrimidine; purine; aminopyrimidine; primary aromatic amine; pyrimidine; monosaccharide; n-substituted imidazole; tetrahydrofuran; imidazole; azole; oxolane; secondary alcohol; 1,2-diol; polyamine; primary alcohol; ether; organonitrogen compound; primary amine; alcohol; amine
Classification descriptionThis compound belongs to the purine nucleosides and analogues. These are compounds comprising a purine base attached to a sugar.
Pharmacology
IndicationFor treatment of chickenpox - varicella, herpes zoster and herpes simplex
PharmacodynamicsVidarabine 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 replication of herpes viral DNA. When used as a substrate for viral DNA polymerase, Vidarabine triphosphate competitively inhibits dATP leading to the formation of 'faulty' DNA. This is where Vidarabine triphosphate is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand.
Mechanism of actionVidarabine 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. This drug is a nucleoside analog and therefore has to be phosphorylated to be active. Vidarabine is sequentially phosphorylated by kinases to the triphosphate ara-ATP. This is the active form of vidarabine and is both an inhibitor and a substrate of viral DNA polymerase. When used as a substrate for viral DNA polymerase, ara-ATP competitively inhibits dATP leading to the formation of ‘faulty’ DNA. This is where ara-ATP is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand
AbsorptionSystemetic absorption of vidarabine should not be expected to occur following ocular administration and swallowing lacrimal secretions.
Volume of distributionNot Available
Protein binding24-38%
Metabolism

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

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityAcute 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9227
Blood Brain Barrier + 0.9383
Caco-2 permeable - 0.8957
P-glycoprotein substrate Non-substrate 0.7026
P-glycoprotein inhibitor I Non-inhibitor 0.966
P-glycoprotein inhibitor II Non-inhibitor 0.9533
Renal organic cation transporter Non-inhibitor 0.9444
CYP450 2C9 substrate Non-substrate 0.8639
CYP450 2D6 substrate Non-substrate 0.8349
CYP450 3A4 substrate Non-substrate 0.5866
CYP450 1A2 substrate Non-inhibitor 0.9667
CYP450 2C9 substrate Non-inhibitor 0.9595
CYP450 2D6 substrate Non-inhibitor 0.977
CYP450 2C19 substrate Non-inhibitor 0.9514
CYP450 3A4 substrate Non-inhibitor 0.962
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9701
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.9182
Biodegradation Not ready biodegradable 0.9738
Rat acute toxicity 1.9715 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.989
hERG inhibition (predictor II) Non-inhibitor 0.9102
Pharmacoeconomics
Manufacturers
  • Parkedale pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
OintmentOphthalmic
Prices
Unit descriptionCostUnit
Vidarabine monohydrate powder687.0USDg
Vidarabine powder366.59USDg
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP-2.115Not Available
Predicted Properties
PropertyValueSource
Water Solubility14.0ALOGPS
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
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00406
KEGG CompoundC07195
PubChem Compound32326
PubChem Substance46506630
ChemSpider29966
ChEBI45327
ChEMBLCHEMBL1090
Therapeutic Targets DatabaseDAP000642
PharmGKBPA451876
HETRAB
RxListhttp://www.rxlist.com/cgi/generic3/vidarabine.htm
Drugs.comhttp://www.drugs.com/mtm/vidarabine-ophthalmic.html
WikipediaVidarabine
ATC CodesJ05AB03S01AD06
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSshow(73.8 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. DNA polymerase catalytic subunit

Kind: protein

Organism: HHV-4

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA polymerase catalytic subunit P03198 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. 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

2. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: incorporation into and destabilization

Components

Name UniProt ID Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

3. Thymidine kinase

Kind: protein

Organism: HHV-3

Pharmacological action: yes

Actions: inducer

Components

Name UniProt ID Details
Thymidine kinase P09250 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. 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
  4. 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
  5. 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

4. Thymidine kinase

Kind: protein

Organism: HHV-1

Pharmacological action: yes

Actions: inducer

Components

Name UniProt ID Details
Thymidine kinase Q9QNF7 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. 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
  4. 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

Enzymes

1. Adenosine deaminase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Adenosine deaminase P00813 Details

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
  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
  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

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08