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
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
Product Ingredients
IngredientUNIICASInChI Key
Cidofovir dihydrateJIL713Q00N149394-66-1FPKARFMSZDBYQF-ILKKLZGPSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VistideInjection75 mg/1mLIntravenousGilead Sciences1996-06-26Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CidofovirInjection, solution75 mg/1mLIntravenousMylan Institutional2013-06-03Not applicableUs
Cidofovir DihydrateInjection, solution375 mg/5mLIntravenousHeritage2012-08-06Not applicableUs
Mar-cidofovirSolution375 mgIntravenousMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
VistideCidofovir (75 mg/ml)Injection, solution, concentrateIntravenousGilead Sciences1997-04-232015-01-19Eu
Categories
UNII
768M1V522C
CAS number
113852-37-2
Weight
Average: 279.187
Monoisotopic: 279.062021707
Chemical Formula
C8H14N3O6P
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

Pharmacology

Indication

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

Associated Conditions
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]
Toxicity

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

Affected organisms
  • Human Immunodeficiency Virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbacavirCidofovir may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseCidofovir may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacCidofovir may decrease the excretion rate of Aceclofenac which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Cidofovir which could result in a higher serum level.
AcetaminophenCidofovir may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideThe excretion of Cidofovir can be decreased when combined with Acetazolamide.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Cidofovir which could result in a higher serum level.
AclidiniumCidofovir may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineCidofovir may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirCidofovir may decrease the excretion rate of Acyclovir which could result in a higher serum level.
Food Interactions
Not Available

References

Synthesis Reference
US5142051
General References
Not Available
External Links
Human Metabolome Database
HMDB0014513
KEGG Compound
C06909
PubChem Compound
60613
PubChem Substance
46506054
ChemSpider
54636
BindingDB
31915
ChEBI
3696
ChEMBL
CHEMBL152
Therapeutic Targets Database
DAP001083
PharmGKB
PA448997
HET
L8P
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cidofovir
ATC Codes
J05AB12 — Cidofovir
AHFS Codes
  • 08:18.32 — Nucleosides and Nucleotides
PDB Entries
2l8p / 5km8
FDA label
Download (828 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentBlood And Marrow Transplantation1
1CompletedTreatmentCervical Cancers1
1CompletedTreatmentCervix Intraepithelial Neoplasia / Uterine Cervical Neoplasms1
1CompletedTreatmentCondylomata Acuminata / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentHerpes Simplex / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentPapilloma1
1Unknown StatusTreatmentCervical Cancers / Precancerous Conditions1
1WithdrawnTreatmentCytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections / Infections, Cytomegalovirus1
1, 2TerminatedTreatmentBK Virus (Nephropathy)1
2Active Not RecruitingTreatmentTransplantation Infection1
2CompletedPreventionPrevention of Hair Growth1
2CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Cytomegalovirus Retinitis1
2CompletedTreatmentAnal Carcinoma / Precancerous Conditions1
2CompletedTreatmentCytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHigh Grade Cervical Epithelial Neoplasia (CIN2+)1
2CompletedTreatmentSarcomas1
2RecruitingTreatmentRecurrent Respiratory Papillomatosis1
2WithdrawnTreatmentWarts1
2, 3CompletedTreatmentCMV Cytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentCytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections1
3RecruitingTreatmentCytomegalovirus (CMV)1
4CompletedTreatmentCytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentRecurrent Respiratory Papillomatosis1
Not AvailableCompletedTreatmentCytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections2
Not AvailableCompletedTreatmentHerpes Simplex / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV)1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Progressive Multifocal Leukoencephalopathy1
Not AvailableRecruitingNot AvailableAcute Bacterial Exacerbation of Chronic Bronchitis (ABECB) / Acute Bacterial Sinusitis (ABS) / Acute Decompensated Heart Failure (ADHF) / Acute Pyelonephritis / Adenovirus / Adjunct to general anesthesia therapy / Adrenal Insufficiency / Airway Swelling / Anaesthesia therapy / Anxiolysis / Arterial Hypotension / Autism, Early Infantile / Autistic Disorder / Bartonellosis / Benzodiazepine Withdrawal / Benzodiazepines / Bipolar Disorder (BD) / Bloodstream Infections / Bone and Joint Infections / Brain Swelling / Bronchospasm / Brucellosis / Cardiac Arrest / Central Nervous System Infections / Cholera / Chronic Bacterial Prostatitis / Community Acquired Pneumonia (CAP) / Complicated Urinary Tract Infections / Convulsions / Cytomegalovirus Retinitis / Drug hypersensitivity reaction / Early-onset Schizophrenia Spectrum Disorders / Edema / Epilepsies / Feeling Anxious / Flu caused by Influenza / Gastroparesis / Gynaecological infection / Headaches / Herpes Simplex Virus / High Blood Pressure (Hypertension) / High Cholesterol / Hospital-acquired bacterial pneumonia / Hyperlipidemias / Infantile Hemangiomas / Infection NOS / Inflammatory Conditions / Inflammatory Reaction / Influenza Treatment or Prophylaxis / Inhalational Anthrax (Post-Exposure) / Intra-Abdominal Infections / Life-threatening Fungal Infections / Lower Respiratory Tract Infection (LRTI) / Meningitis, Bacterial / Migraines / Muscle Spasms / Nausea / Opioid Addiction / Pain NOS / Plague / Pneumonia / Prophylaxis / Psittacosis / Q Fever / Reflux / Relapsing Fever / Rocky Mountain Spotted Fever / Schizophrenic Disorders / Sedation therapy / Seizures / Sepsis / Skeletal Muscle Spasms / Skin and Subcutaneous Tissue Bacterial Infections / Skin Structures and Soft Tissue Infections / Stable Angina (SA) / Thromboprophylaxis / Thrombotic events / Toxic effect of hydrocyanic acid and cyanides / Trachoma / Treatment-resistant Schizophrenia / Tularemia / Typhus Fever / Uncomplicated Skin and Skin Structure Infections / Uncomplicated Urinary Tract Infections / Urinary Tract Infections (UTIs) / Vomiting / Withdrawal1
Not AvailableUnknown StatusTreatmentCytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableWithdrawnTreatmentBladder Diseases / Cystitis1

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
SolutionIntravenous375 mg
InjectionIntravenous75 mg/1mL
Injection, solution, concentrateIntravenous75 mg/ml
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)
US5142051No1992-08-252010-06-26Us
CA1340856No1999-12-212016-12-21Canada

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-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 Area145.68 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-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

Taxonomy

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
Aminopyrimidine / Pyrimidone / Hydropyrimidine / Imidolactam / Organophosphonic acid / Organophosphonic acid derivative / Heteroaromatic compound / Azacycle / Organic oxide / Organopnictogen compound
show 11 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyrimidone, phosphonic acids (CHEBI:3696)

Targets

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. [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. 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:16048917]
  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. [PubMed:17913252]
  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:16304146]
  6. Andrei G, De Clercq E, Snoeck R: Drug targets in cytomegalovirus infection. Infect Disord Drug Targets. 2009 Apr;9(2):201-22. [PubMed:19275707]

Enzymes

Kind
Protein
Organism
Human
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. [PubMed:19844936]

Transporters

Kind
Protein
Organism
Human
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. [PubMed:10929807]
  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:10462545]
  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:10703662]

Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 03:11