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targets (1) transporters (1)
for drugs
Identification
Name Cidofovir
Accession Number DB00369 (APRD00148)
Type small molecule
Groups approved
Description

Cidofovir is an injectable antiviral medication for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. It suppresses CMV replication by selective inhibition of viral DNA synthesis. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • CDV
  • Cidofovir Anhydrous
Brand names
  • HPMPC
  • Vistide
Brand name mixtures Not Available
Categories
  • Antineoplastic Agents
  • Antiviral Agents
  • Anti-HIV Agents
  • Radiation-Sensitizing Agents
CAS number 113852-37-2
Weight Average: 279.187
Monoisotopic: 279.062021707
Chemical Formula C8H14N3O6P
InChI Key InChIKey=VWFCHDSQECPREK-LURJTMIESA-N
InChI
InChI=1S/C8H14N3O6P/c9-7-1-2-11(8(13)10-7)3-6(4-12)17-5-18(14,15)16/h1-2,6,12H,3-5H2,(H2,9,10,13)(H2,14,15,16)/t6-/m0/s1
Plain Text
IUPAC Name
({[(2S)-1-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3-hydroxypropan-2-yl]oxy}methyl)phosphonic acid
SMILES
NC1=NC(=O)N(C[C@@H](CO)OCP(O)(O)=O)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Pyrimidines and Derivatives
Substructures
  • Hydroxy Compounds
  • Phosphonic Acids and Derivatives
  • Aliphatic and Aryl Amines
  • Ethers
  • Alcohols and Polyols
  • Pyrimidines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Phosphinic Acids and Derivatives
  • Cyanamides
Pharmacology
Indication For the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS)
Pharmacodynamics Cidofovir is a new anti-viral drug. It is classified as a nucleotide analogue and is active against herpes cytomegalovirus (CMV) retinitis infection. Most adults are infected with CMV. Cidofovir suppresses cytomegalovirus (CMV) replication by selective inhibition of viral DNA synthesis.
Mechanism of action Cidofovir acts through the selective inhibition of viral DNA polymerase.Biochemical data support selective inhibition of CMV DNA polymerase by cidofovir diphosphate, the active intracellular metabolite of cidofovir. Cidofovir diphosphate inhibits herpesvirus polymerases at concentrations that are 8- to 600-fold lower than those needed to inhibit human cellular DNA polymerase alpha, beta, and gamma(1,2,3). Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis.
Absorption 100%
Volume of distribution
  • 537 ± 126 mL/kg [VISTIDE ADMINISTERED WITHOUT PROBENECID]
  • 410 ± 102 mL/kg [VISTIDE ADMINISTERED WITH PROBENECID]
Protein binding 6%
Metabolism
Route of elimination Not Available
Half life 2.4 to 3.2 hours
Clearance
  • 179 +/- 23.1 mL/min/1.73 m2 [WITHOUT PROBENECID]
  • 148 +/- 38.8 mL/min/1.73 m2 [WITH PROBENECID]
Toxicity Kidney damage, fall in the number of white blood cells, decreased platelets
Affected organisms
  • Human Immunodeficiency Virus
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Gilead sciences inc
Packagers
Dosage forms
Form Route Strength
Solution Intravenous
Prices
Unit description Cost Unit
Vistide 75 mg/ml Solution 5ml Vial 923.52 USD vial
Vistide 75 mg/ml vial 205.71 USD ml
Patents
Country Patent Number Approved Expires
United States 5142051 1993-06-26 2010-06-26
Canada 1340856 1999-12-21 2016-12-21
Properties
State solid
Melting point 480 oC
Experimental Properties
Property Value Source
water solubility =170 mg/mL at pH 6-8 PhysProp
logP -3.9 PhysProp
Predicted Properties
Property Value Source
water solubility 1.15e+01 g/l ALOGPS
logP -2.12 ALOGPS
logP -4.15 ChemAxon Molconvert
logS -1.38 ALOGPS
pKa 7.90 ChemAxon Molconvert
hydrogen acceptor count 8 ChemAxon Molconvert
hydrogen donor count 4 ChemAxon Molconvert
polar surface area 145.68 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 60.43 ChemAxon Molconvert
polarizability 24.40 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C06909 Link_out
PubChem Compound 60613 Link_out
PubChem Substance 46506054 Link_out
ChemSpider 54636 Link_out
BindingDB 31915 Link_out
ChEBI 3696 Link_out
ChEMBL 3696 Link_out
Therapeutic Targets Database DAP001083 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic2/cidofovir.htm Link_out
Drugs.com http://www.drugs.com/cdi/cidofovir.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Cidofovir Link_out
ATC Codes
  • J05AB12
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (828.4 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Food Interactions Not Available
Targets

1. DNA polymerase

Pharmacological action: yes
Actions: inhibitor
Organism class: viral
UniProt ID: P08546 Link_out
Gene: UL54
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. Magee WC, Hostetler KY, Evans DH: Mechanism of inhibition of vaccinia virus DNA polymerase by cidofovir diphosphate. Antimicrob Agents Chemother. 2005 Aug;49(8):3153-62. Pubmed
  4. Sergerie Y, Boivin G: Hydroxyurea enhances the activity of acyclovir and cidofovir against herpes simplex virus type 1 resistant strains harboring mutations in the thymidine kinase and/or the DNA polymerase genes. Antiviral Res. 2007 Sep 17;. Pubmed
  5. Gilbert C, Boivin G: New reporter cell line to evaluate the sequential emergence of multiple human cytomegalovirus mutations during in vitro drug exposure. Antimicrob Agents Chemother. 2005 Dec;49(12):4860-6. Pubmed
  6. Andrei G, De Clercq E, Snoeck R: Drug targets in cytomegalovirus infection. Infect Disord Drug Targets. 2009 Apr;9(2):201-22. Pubmed
Transporters

1. Solute carrier family 22 member 6

Actions: substrate, inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cihlar T, Ho ES: Fluorescence-based assay for the interaction of small molecules with the human renal organic anion transporter 1. Anal Biochem. 2000 Jul 15;283(1):49-55. Pubmed
  2. Cihlar T, Lin DC, Pritchard JB, Fuller MD, Mendel DB, Sweet DH: The antiviral nucleotide analogs cidofovir and adefovir are novel substrates for human and rat renal organic anion transporter 1. Mol Pharmacol. 1999 Sep;56(3):570-80. Pubmed
  3. Ho ES, Lin DC, Mendel DB, Cihlar T: Cytotoxicity of antiviral nucleotides adefovir and cidofovir is induced by the expression of human renal organic anion transporter 1. J Am Soc Nephrol. 2000 Mar;11(3):383-93. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on September 03, 2011 16:32

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.