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Identification
NameCidofovir
Accession NumberDB00369  (APRD00148)
Typesmall molecule
Groupsapproved
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
Synonyms
SynonymLanguageCode
({[(S)-1-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3-hydroxypropan-2-yl]oxy}methyl)phosphonic acidNot AvailableIUPAC
(S)-(3-(4-amino-2-Oxopyrimidin-1(2H)-yl)-1-hydroxypropan-2-yloxy)methylphosphonic acidNot AvailableNot Available
(S)-1-(3-Hydroxy-2-phosphonomethoxypropyl)cytosineNot AvailableNot Available
(S)-1-[3-Hydroxy-2-(phosphonomethoxy)propyl]cytosineNot AvailableNot Available
(S)-1-[3-Hydroxy-2-(phosphonylmethoxy)propyl]cytosineNot AvailableNot Available
(S)-HPMPCNot AvailableNot Available
[(S)-2-(4-Amino-2-oxo-2H-pyrimidin-1-yl)-1-hydroxymethyl-ethoxymethyl]-phosphonic acidNot AvailableNot Available
[[(S)-2-(4-amino-2-oxo-1(2H)-pyrimidinyl)-1-(hydroxymethyl)ethoxy]methyl]phosphonic acid Not AvailableWHO
1-(S)-[3-Hydroxy-2-(phosphonomethoxy)propyl]cytosineNot AvailableNot Available
1-[(S)-3-Hydroxy-2-(phosphonomethoxy)propyl]cytosineNot AvailableNot Available
CDVNot AvailableNot Available
CidofovirNot AvailableDCF, USAN, BAN
Cidofovir anhydrousNot AvailableNot Available
CidofovirumLatinINN
SaltsNot Available
Brand names
NameCompany
VistideGilead
Brand mixturesNot Available
Categories
CAS number113852-37-2
WeightAverage: 279.187
Monoisotopic: 279.062021707
Chemical FormulaC8H14N3O6P
InChI KeyVWFCHDSQECPREK-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
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassDiazines
SubclassPyrimidines and Pyrimidine Derivatives
Direct parentPyrimidones
Alternative parentsAminopyrimidines and Derivatives; Primary Aromatic Amines; Hydropyrimidines; Organic Phosphonic Acids; Primary Alcohols; Ethers; Polyamines
Substituentshydropyrimidine; primary aromatic amine; phosphonic acid; phosphonic acid derivative; ether; polyamine; primary alcohol; amine; primary amine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the pyrimidones. These are compounds whose pyrimidine ring bears a ketone.
Pharmacology
IndicationFor the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS)
PharmacodynamicsCidofovir 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 actionCidofovir 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.
Absorption100%
Volume of distribution
  • 537 ± 126 mL/kg [VISTIDE ADMINISTERED WITHOUT PROBENECID]
  • 410 ± 102 mL/kg [VISTIDE ADMINISTERED WITH PROBENECID]
Protein binding6%
Metabolism
Route of eliminationNot Available
Half life2.4 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]
ToxicityKidney damage, fall in the number of white blood cells, decreased platelets
Affected organisms
  • Human Immunodeficiency Virus
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.9299
Blood Brain Barrier + 0.9061
Caco-2 permeable - 0.6933
P-glycoprotein substrate Non-substrate 0.5589
P-glycoprotein inhibitor I Non-inhibitor 0.8796
P-glycoprotein inhibitor II Non-inhibitor 0.9247
Renal organic cation transporter Non-inhibitor 0.9415
CYP450 2C9 substrate Non-substrate 0.791
CYP450 2D6 substrate Non-substrate 0.839
CYP450 3A4 substrate Non-substrate 0.6246
CYP450 1A2 substrate Non-inhibitor 0.8679
CYP450 2C9 substrate Non-inhibitor 0.8338
CYP450 2D6 substrate Non-inhibitor 0.8796
CYP450 2C19 substrate Non-inhibitor 0.8039
CYP450 3A4 substrate Non-inhibitor 0.941
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9492
Ames test Non AMES toxic 0.5853
Carcinogenicity Non-carcinogens 0.8317
Biodegradation Not ready biodegradable 0.9148
Rat acute toxicity 2.3450 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9371
hERG inhibition (predictor II) Non-inhibitor 0.6893
Pharmacoeconomics
Manufacturers
  • Gilead sciences inc
Packagers
Dosage forms
FormRouteStrength
SolutionIntravenous
Prices
Unit descriptionCostUnit
Vistide 75 mg/ml Solution 5ml Vial923.52USDvial
Vistide 75 mg/ml vial205.71USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States51420511993-06-262010-06-26
Canada13408561999-12-212016-12-21
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point480 °CNot Available
water solubility=170 mg/mL at pH 6-8Not Available
logP-3.9Not Available
Predicted Properties
PropertyValueSource
water solubility1.15e+01 g/lALOGPS
logP-2.1ALOGPS
logP-3.4ChemAxon
logS-1.4ALOGPS
pKa (strongest acidic)1.19ChemAxon
pKa (strongest basic)2.15ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count8ChemAxon
hydrogen donor count4ChemAxon
polar surface area145.68ChemAxon
rotatable bond count6ChemAxon
refractivity60.43ChemAxon
polarizability24.44ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US5142051
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00273
KEGG CompoundC06909
PubChem Compound60613
PubChem Substance46506054
ChemSpider54636
BindingDB31915
ChEBI3696
ChEMBLCHEMBL152
Therapeutic Targets DatabaseDAP001083
PharmGKBPA448997
RxListhttp://www.rxlist.com/cgi/generic2/cidofovir.htm
Drugs.comhttp://www.drugs.com/cdi/cidofovir.html
WikipediaCidofovir
ATC CodesJ05AB12
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(828 KB)
MSDSNot Available
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. DNA polymerase catalytic subunit

Kind: protein

Organism: HHV-5

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA polymerase catalytic subunit P08546 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. 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

Enzymes

1. Thymidine phosphorylase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Thymidine phosphorylase P19971 Details

References:

  1. De Clercq E: The next ten stories on antiviral drug discovery (part E): advents, advances, and adventures. Med Res Rev. 2011 Jan;31(1):118-60. doi: 10.1002/med.20179. Pubmed

Transporters

1. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

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

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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:22