Identification

Name
Vidarabine
Accession Number
DB00194  (APRD00333, EXPT02753)
Type
Small Molecule
Groups
Approved, Investigational
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
  • 2-(6-AMINO-purin-9-yl)-5-hydroxymethyl-tetrahydro-furan-3,4-diol
  • 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
International/Other Brands
Arasena-A / Vira-A
Categories
UNII
3XQD2MEW34
CAS number
24356-66-9
Weight
Average: 267.2413
Monoisotopic: 267.096753929
Chemical Formula
C10H13N5O4
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

Pharmacology

Indication

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

Structured Indications
Not Available
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 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 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. 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

TargetActionsOrganism
ADNA polymerase catalytic subunit
inhibitor
HHV-4
ADNA
incorporation into and destabilization
Human
AThymidine kinase
inducer
HHV-3
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
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
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB14340
KEGG Drug
D00406
KEGG Compound
C07195
PubChem Compound
21704
PubChem Substance
46506630
ChemSpider
20400
BindingDB
50144936
ChEBI
45327
ChEMBL
CHEMBL1090
Therapeutic Targets Database
DAP000642
PharmGKB
PA451876
HET
RAB
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Vidarabine
ATC Codes
J05AB03 — VidarabineS01AD06 — 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
Dosage forms
Not Available
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

Taxonomy

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
Purine nucleoside / Glycosyl compound / N-glycosyl compound / 6-aminopurine / Pentose monosaccharide / Imidazopyrimidine / Purine / Aminopyrimidine / Monosaccharide / N-substituted imidazole
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
purine nucleoside, beta-D-arabinoside (CHEBI:45327)

Targets

Kind
Protein
Organism
HHV-4
Pharmacological action
Yes
Actions
Inhibitor
General Function
Nucleotide binding
Specific Function
Replicates viral genomic DNA in the late phase of lytic infection, producing long concatemeric DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity facto...
Gene Name
Not Available
Uniprot ID
P03198
Uniprot Name
DNA polymerase catalytic subunit
Molecular Weight
113417.06 Da
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:17139284]
  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:17016423]
  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:16797734]
2. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Incorporation into and destabilization
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
HHV-3
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  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:17016423]
  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:16797734]
  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:12122323]
  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: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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  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:17016423]
  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:16797734]
  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:12122323]

Enzymes

Kind
Protein
Organism
Human
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 November 07, 2017 01:34