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Identification
Name Vidarabine
Accession Number DB00194 (APRD00333, EXPT02753)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • 9-beta-D-arabinofuranosyl-adenine
  • Adenine Arabinoside
  • Ara Atp
  • Ara-A
  • Ara-a Triphosphate
  • Ara-Atp
  • Araadenosine
  • Arabinofuranosyladenine Triphosphate
  • Arabinoside Adenine
  • Arabinosyl Adenine
  • Arabinosyl-Atp
  • Arabinosyladenine
  • Arabinosyladenine Triphosphate
  • Vidarabine Triphosphate
Brand names
  • Arasena-A
  • Spongoadenosine
  • Vidarabin
  • Vira-A
Brand name mixtures Not Available
Categories
  • Antiviral Agents
  • Antimetabolites
CAS number 24356-66-9
Weight Average: 285.2566
Monoisotopic: 285.107318615
Chemical Formula C10H15N5O5
InChI Key InChIKey=ZTHWFVSEMLMLKT-CAMOTBBTSA-N
InChI
InChI=1S/C10H13N5O4.H2O/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);1H2/t4-,6-,7+,10-;/m1./s1
Plain Text
IUPAC Name
(2R,3S,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol hydrate
SMILES
O.NC1=NC=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Purines and Purine Derivatives
  • Carbohydrates
Substructures
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Aliphatic and Aryl Amines
  • Ethers
  • Alcohols and Polyols
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Furans
  • Cyanamides
  • Carbohydrates
Pharmacology
Indication For treatment of chickenpox - varicella, herpes zoster and herpes simplex
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
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
Pharmacoeconomics
Manufacturers
  • Parkedale pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Ointment Ophthalmic
Prices
Unit description Cost Unit
Vidarabine monohydrate powder 687.0 USD g
Vidarabine powder 366.59 USD g
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
logP -2.115 PhysProp
Predicted Properties
Property Value Source
water solubility ALOGPS
logP ALOGPS
logP -2.09 ChemAxon Molconvert
logS ALOGPS
pKa 13.89 ChemAxon Molconvert
hydrogen acceptor count 8 ChemAxon Molconvert
hydrogen donor count 4 ChemAxon Molconvert
polar surface area 139.54 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 63.20 ChemAxon Molconvert
polarizability 24.49 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00406 Link_out
KEGG Compound C07195 Link_out
PubChem Compound 32326 Link_out
PubChem Substance 46506630 Link_out
ChemSpider 29966 Link_out
ChEBI 45327 Link_out
ChEMBL 45327 Link_out
Therapeutic Targets Database DAP000642 Link_out
PharmGKB PA451876 Link_out
HET RAB Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic3/vidarabine.htm Link_out
Drugs.com http://www.drugs.com/mtm/vidarabine-ophthalmic.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Vidarabine Link_out
ATC Codes
  • J05AB03
  • S01AD06
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS show (73.8 KB)
Interactions
Drug Interactions
Drug Interaction
Food Interactions Not Available
Targets

1. DNA polymerase

Pharmacological action: yes
Actions: inhibitor

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)

Organism class: viral
UniProt ID: P03198 Link_out
Gene: BALF5
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: incorporation into and destabilization

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.

Gene Sequence: FASTA

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

Pharmacological action: yes
Actions: inducer
Organism class: viral
UniProt ID: P09250 Link_out
Gene: ORF36
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inducer

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 their genome

Organism class: viral
UniProt ID: Q9QNF7 Link_out
Gene: TK
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Adenosine + H(2)O = inosine + NH(3)

UniProt ID: P00813 Link_out
Gene: ADA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Drug created on June 13, 2005 07:24 / Updated on July 25, 2011 11:44

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.