Cidofovir

Identification

Summary

Cidofovir is an antiviral agent used to treat Cytomegalovirus (CMV) retinitis in patients with AIDS.

Brand Names
Vistide
Generic Name
Cidofovir
DrugBank Accession Number
DB00369
Background

Cidofovir is an injectable antiviral medication employed in the treatment of cytomegalovirus (CMV) retinitis in patients diagnosed with AIDS. It suppresses CMV replication through selective inhibition of viral DNA synthesis.Label It was manufactured by Gilead and initially approved by the FDA in 1996, but has since been discontinued.1

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 279.187
Monoisotopic: 279.062021707
Chemical Formula
C8H14N3O6P
Synonyms
  • ({[(S)-1-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3-hydroxypropan-2-yl]oxy}methyl)phosphonic acid
  • (S)-(3-(4-amino-2-Oxopyrimidin-1(2H)-yl)-1-hydroxypropan-2-yloxy)methylphosphonic acid
  • (S)-1-(3-Hydroxy-2-phosphonomethoxypropyl)cytosine
  • (S)-1-[3-Hydroxy-2-(phosphonomethoxy)propyl]cytosine
  • (S)-1-[3-Hydroxy-2-(phosphonylmethoxy)propyl]cytosine
  • (S)-HPMPC
  • [(S)-2-(4-Amino-2-oxo-2H-pyrimidin-1-yl)-1-hydroxymethyl-ethoxymethyl]-phosphonic acid
  • [[(S)-2-(4-amino-2-oxo-1(2H)-pyrimidinyl)-1-(hydroxymethyl)ethoxy]methyl]phosphonic acid
  • 1-(S)-[3-Hydroxy-2-(phosphonomethoxy)propyl]cytosine
  • 1-[(S)-3-Hydroxy-2-(phosphonomethoxy)propyl]cytosine
  • CDV
  • Cidofovir
  • Cidofovir anhydrous
  • Cidofovirum
External IDs
  • GS 0504
  • GS 504
  • HPMPC

Pharmacology

Indication

For the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS)

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofCytomegalovirus retinitis••••••••••••
Treatment ofHerpes simplex virus••• •••••••••••••• ••••••••••
Treatment ofMonkeypox••• •••••
Treatment ofSmallpox••• •••••
Contraindications & Blackbox Warnings
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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.

TargetActionsOrganism
ADNA polymerase catalytic subunit
inhibitor
HHV-5
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
Not Available
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]
Adverse Effects
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Toxicity

Kidney damage, fall in the number of white blood cells, decreased platelets

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirCidofovir may decrease the excretion rate of Abacavir which could result in a higher serum level.
AceclofenacThe risk or severity of nephrotoxicity can be increased when Cidofovir is combined with Aceclofenac.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Cidofovir is combined with Acemetacin.
AcetaminophenCidofovir may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Cidofovir which could result in a lower serum level and potentially a reduction in efficacy.
Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Cidofovir dihydrateJIL713Q00N149394-66-1FPKARFMSZDBYQF-ILKKLZGPSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
VistideInjection75 mg/1mLIntravenousGilead Sciences1996-06-26Not applicableUS flag
VistideInjection, solution, concentrate75 mg/mlIntravenousGilead Sciences2016-09-082015-01-19EU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CidofovirInjection, solution75 mg/1mLIntravenousMylan Institutional LLC2013-06-03Not applicableUS flag
Cidofovir DihydrateInjection, solution375 mg/5mLIntravenousHeritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.2012-08-06Not applicableUS flag
Mar-cidofovirSolution375 mg / 5 mLIntravenousMarcan Pharmaceuticals Inc2018-07-11Not applicableCanada flag

Categories

ATC Codes
J05AB12 — Cidofovir
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pyrimidones. These are compounds that contain a pyrimidine ring, which bears a ketone. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrimidines and pyrimidine derivatives
Direct Parent
Pyrimidones
Alternative Parents
Aminopyrimidines and derivatives / Imidolactams / Hydropyrimidines / Organic phosphonic acids / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Primary alcohols / Organopnictogen compounds / Organophosphorus compounds
show 2 more
Substituents
Alcohol / Amine / Aminopyrimidine / Aromatic heteromonocyclic compound / Azacycle / Heteroaromatic compound / Hydrocarbon derivative / Hydropyrimidine / Imidolactam / Organic nitrogen compound
show 11 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyrimidone, phosphonic acids (CHEBI:3696)
Affected organisms
  • Human Immunodeficiency Virus

Chemical Identifiers

UNII
768M1V522C
CAS number
113852-37-2
InChI Key
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
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

References

Synthesis Reference
US5142051
General References
  1. Cidofovir FDA approval [Link]
Human Metabolome Database
HMDB0014513
KEGG Compound
C06909
PubChem Compound
60613
PubChem Substance
46506054
ChemSpider
54636
BindingDB
31915
RxNav
1546007
ChEBI
3696
ChEMBL
CHEMBL152
ZINC
ZINC000001530600
Therapeutic Targets Database
DAP001083
PharmGKB
PA448997
PDBe Ligand
L8P
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cidofovir
PDB Entries
2l8p / 5km8
FDA label
Download (828 KB)

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
  • Gilead sciences inc
Packagers
  • Gilead Sciences Inc.
  • Pfizer Inc.
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous75 mg/1mL
Injection, solutionIntravenous375 mg/5mL
Injection, solution, concentrateIntravenous375 mg/5ml
Injection, solution, concentrateIntravenous75 MG/ML
SolutionIntravenous375 mg / 5 mL
InjectionIntravenous375 mg/5ml
InjectionIntravenous75 mg/1mL
Prices
Unit descriptionCostUnit
Vistide 75 mg/ml Solution 5ml Vial923.52USD vial
Vistide 75 mg/ml vial205.71USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5142051No1992-08-252010-06-26US flag
CA1340856No1999-12-212016-12-21Canada flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)480 °CNot Available
water solubility=170 mg/mL at pH 6-8Not Available
logP-3.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility11.5 mg/mLALOGPS
logP-2.1ALOGPS
logP-2.4Chemaxon
logS-1.4ALOGPS
pKa (Strongest Acidic)1.26Chemaxon
pKa (Strongest Basic)4.71Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count8Chemaxon
Hydrogen Donor Count4Chemaxon
Polar Surface Area145.68 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity60.43 m3·mol-1Chemaxon
Polarizability24.44 Å3Chemaxon
Number of Rings1Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.9299
Blood Brain Barrier+0.9061
Caco-2 permeable-0.6933
P-glycoprotein substrateNon-substrate0.5589
P-glycoprotein inhibitor INon-inhibitor0.8796
P-glycoprotein inhibitor IINon-inhibitor0.9247
Renal organic cation transporterNon-inhibitor0.9415
CYP450 2C9 substrateNon-substrate0.791
CYP450 2D6 substrateNon-substrate0.839
CYP450 3A4 substrateNon-substrate0.6246
CYP450 1A2 substrateNon-inhibitor0.8679
CYP450 2C9 inhibitorNon-inhibitor0.8338
CYP450 2D6 inhibitorNon-inhibitor0.8796
CYP450 2C19 inhibitorNon-inhibitor0.8039
CYP450 3A4 inhibitorNon-inhibitor0.941
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9492
Ames testNon AMES toxic0.5853
CarcinogenicityNon-carcinogens0.8317
BiodegradationNot ready biodegradable0.9148
Rat acute toxicity2.3450 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9371
hERG inhibition (predictor II)Non-inhibitor0.6893
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-MSsplash10-003r-9820000000-aa7cf1e5b61efad3d0f9
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-0190000000-7ee4511de008b50f3656
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004r-0090000000-40b4a2aa1472152a0c84
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-1190000000-2e3fcb0d0b15c3c0f120
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0910000000-f79728a81c6cd5d631ef
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-016u-9010000000-c10710084e8458849375
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0wna-9200000000-f89f20c28bbc5b885f99
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-167.0009265
predicted
DarkChem Lite v0.1.0
[M-H]-168.2468265
predicted
DarkChem Lite v0.1.0
[M-H]-156.63863
predicted
DeepCCS 1.0 (2019)
[M+H]+166.3120265
predicted
DarkChem Lite v0.1.0
[M+H]+167.9942265
predicted
DarkChem Lite v0.1.0
[M+H]+158.99663
predicted
DeepCCS 1.0 (2019)
[M+Na]+166.7413265
predicted
DarkChem Lite v0.1.0
[M+Na]+167.3604265
predicted
DarkChem Lite v0.1.0
[M+Na]+165.08977
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
HHV-5
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
UL54
Uniprot ID
P08546
Uniprot Name
DNA polymerase catalytic subunit
Molecular Weight
137100.705 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. [Article]
  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. [Article]
  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. [Article]
  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. 2008 Jan;77(1):77-80. Epub 2007 Sep 17. [Article]
  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. [Article]
  6. Andrei G, De Clercq E, Snoeck R: Drug targets in cytomegalovirus infection. Infect Disord Drug Targets. 2009 Apr;9(2):201-22. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transferase activity, transferring pentosyl groups
Specific Function
May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in v...
Gene Name
TYMP
Uniprot ID
P19971
Uniprot Name
Thymidine phosphorylase
Molecular Weight
49954.965 Da
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. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
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. [Article]
  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. [Article]
  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. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48