Cidofovir
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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)
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Cytomegalovirus retinitis •••••••••••• Treatment of Herpes simplex virus ••• ••••• ••••••••• •••••••••• Treatment of Monkeypox ••• ••••• Treatment of Smallpox ••• ••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- 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.
Target Actions Organism ADNA polymerase catalytic subunit modulatorHHV-1 ADNA polymerase catalytic subunit inhibitorHHV-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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Cidofovir may decrease the excretion rate of Abacavir which could result in a higher serum level. Acamprosate The excretion of Acamprosate can be decreased when combined with Cidofovir. Aceclofenac The risk or severity of nephrotoxicity can be increased when Cidofovir is combined with Aceclofenac. Acemetacin The risk or severity of nephrotoxicity can be increased when Cidofovir is combined with Acemetacin. Acetaminophen Cidofovir may decrease the excretion rate of Acetaminophen which could result in a higher serum level. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Cidofovir dihydrate JIL713Q00N 149394-66-1 FPKARFMSZDBYQF-ILKKLZGPSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Vistide Injection, solution, concentrate 75 mg/ml Intravenous Gilead Sciences 2016-09-08 2014-08-22 EU Vistide Injection 75 mg/1mL Intravenous Gilead Sciences 1996-06-26 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Cidofovir Injection, solution 75 mg/1mL Intravenous Mylan Institutional Inc. 2013-06-03 Not applicable US Cidofovir Dihydrate Injection, solution 375 mg/5mL Intravenous Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc. 2012-08-06 Not applicable US Mar-cidofovir Solution 375 mg / 5 mL Intravenous Marcan Pharmaceuticals Inc 2018-07-11 Not applicable Canada
Categories
- ATC Codes
- J05AB12 — Cidofovir
- Drug Categories
- Anti-Infective Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Cytomegalovirus Nucleoside Analog DNA Polymerase Inhibitor
- Cytosine
- Direct Acting Antivirals
- Drugs that are Mainly Renally Excreted
- Enzyme Inhibitors
- Nephrotoxic agents
- Nucleic Acid Synthesis Inhibitors
- Nucleosides and Nucleotides
- Nucleosides and Nucleotides Excl. Reverse Transcriptase Inhibitors
- OAT1/SLC22A6 inhibitors
- OAT1/SLC22A6 Substrates
- Organophosphonates
- Organophosphorus Compounds
- Pyrimidines
- Pyrimidinones
- 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
- Cidofovir FDA approval [Link]
- External Links
- Human Metabolome Database
- HMDB0014513
- KEGG Compound
- C06909
- PubChem Compound
- 60613
- PubChem Substance
- 46506054
- ChemSpider
- 54636
- BindingDB
- 31915
- 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 / 9f3d
- FDA label
- Download (828 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
Pharmacoeconomics
- Manufacturers
- Gilead sciences inc
- Packagers
- Gilead Sciences Inc.
- Pfizer Inc.
- Physicians Total Care Inc.
- Dosage Forms
Form Route Strength Injection, solution Intravenous 75 mg/1mL Injection, solution Intravenous 375 mg/5mL Injection, solution, concentrate Intravenous 375 mg/5ml Injection, solution, concentrate Intravenous 75 MG/ML Solution Intravenous 375 mg / 5 mL Injection Intravenous 375 mg/5ml Injection Intravenous 75 mg/1mL - Prices
Unit description Cost Unit Vistide 75 mg/ml Solution 5ml Vial 923.52USD vial Vistide 75 mg/ml vial 205.71USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5142051 No 1992-08-25 2010-06-26 US CA1340856 No 1999-12-21 2016-12-21 Canada
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 480 °C Not Available water solubility =170 mg/mL at pH 6-8 Not Available logP -3.9 Not Available - Predicted Properties
Property Value Source Water Solubility 11.5 mg/mL ALOGPS logP -2.1 ALOGPS logP -2.4 Chemaxon logS -1.4 ALOGPS pKa (Strongest Acidic) 1.26 Chemaxon pKa (Strongest Basic) 4.71 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 145.68 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 60.43 m3·mol-1 Chemaxon Polarizability 24.44 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - 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 inhibitor Non-inhibitor 0.8338 CYP450 2D6 inhibitor Non-inhibitor 0.8796 CYP450 2C19 inhibitor Non-inhibitor 0.8039 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-003r-9820000000-aa7cf1e5b61efad3d0f9 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-0190000000-7ee4511de008b50f3656 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004r-0090000000-40b4a2aa1472152a0c84 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-1190000000-2e3fcb0d0b15c3c0f120 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0910000000-f79728a81c6cd5d631ef Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-016u-9010000000-c10710084e8458849375 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0wna-9200000000-f89f20c28bbc5b885f99 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 167.0009265 predictedDarkChem Lite v0.1.0 [M-H]- 168.2468265 predictedDarkChem Lite v0.1.0 [M-H]- 156.63863 predictedDeepCCS 1.0 (2019) [M+H]+ 166.3120265 predictedDarkChem Lite v0.1.0 [M+H]+ 167.9942265 predictedDarkChem Lite v0.1.0 [M+H]+ 158.99663 predictedDeepCCS 1.0 (2019) [M+Na]+ 166.7413265 predictedDarkChem Lite v0.1.0 [M+Na]+ 167.3604265 predictedDarkChem Lite v0.1.0 [M+Na]+ 165.08977 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- HHV-1
- Pharmacological action
- Yes
- Actions
- Modulator
- General Function
- Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding protein. Additionally, the polymerase contains an intrinsic ribonuclease H (RNase H) activity that specifically degrades RNA/DNA heteroduplexes or duplex DNA substrates in the 5' to 3' direction. Therefore, it can catalyze the excision of the RNA primers that initiate the synthesis of Okazaki fragments at a replication fork during viral DNA replication.
- Specific Function
- 3'-5'-DNA exonuclease activity
- Gene Name
- Not Available
- Uniprot ID
- P04293
- Uniprot Name
- DNA polymerase catalytic subunit
- Molecular Weight
- 136419.66 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- HHV-5
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 factor, primase, primase-associated factor, helicase, and ssDNA-binding protein (By similarity).
- Specific Function
- 3'-5'-DNA exonuclease activity
- Gene Name
- UL54
- Uniprot ID
- P08546
- Uniprot Name
- DNA polymerase catalytic subunit
- Molecular Weight
- 137100.705 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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]
- 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]
- 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]
- 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]
- 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
- 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 vitro
- Specific Function
- 1,4-alpha-oligoglucan phosphorylase activity
- Gene Name
- TYMP
- Uniprot ID
- P19971
- Uniprot Name
- Thymidine phosphorylase
- Molecular Weight
- 49954.965 Da
References
- 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
- SubstrateInhibitor
- General Function
- Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
- Specific Function
- alpha-ketoglutarate transmembrane transporter activity
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- 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]
- 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]
- 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 October 29, 2024 18:00