DrugBank: Foscarnet (DB00529)

targets (2) transporters (2)

Identification

Name

Foscarnet

Accession Number

DB00529 (APRD00669)

Type

small molecule

Groups

approved

Description

An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV. [PubChem]

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Carboxyphosphonic acid
Dihydroxyphosphinecarboxylic acid oxide
Forscarnet sodium
Foscarnet sodium
PFA
Phgosphonocarboxylic acid
Phosphonoformate
Phosphonoformic acid

Brand names

Foscarmet
Foscavir
Triapten

Brand name mixtures

Not Available

Categories

Antiviral Agents
Reverse Transcriptase Inhibitors

CAS number

63585-09-1

Weight

Average: 126.0053
Monoisotopic: 125.971809718

Chemical Formula

CH₃O₅P

InChI Key

InChIKey=ZJAOAACCNHFJAH-UHFFFAOYSA-N

InChI

InChI=1S/CH3O5P/c2-1(3)7(4,5)6/h(H,2,3)(H2,4,5,6)

Plain Text

IUPAC Name

phosphonoformic acid

SMILES

OC(=O)P(O)(O)=O

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Phosphonic Acids and Derivatives

Substructures

Hydroxy Compounds
Phosphonic Acids and Derivatives
Phosphinic Acids and Derivatives

Pharmacology

Indication

For the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) and for treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients.

Pharmacodynamics

Foscarnet is an organic analogue of inorganic pyrophosphate that inhibits replication of herpes viruses in vitro including cytomegalovirus (CMV) and herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). Foscarnet does not require activation (phosphorylation) by thymidine kinase or other kinases and therefore is active in vitro against HSV TK deficient mutants and CMV UL97 mutants. Thus, HSV strains resistant to acyclovir or CMV strains resistant to ganciclovir may be sensitive to foscarnet. However, acyclovir or ganciclovir resistant mutants with alterations in the viral DNA polymerase may be resistant to foscarnet and may not respond to therapy with foscarnet. The combination of foscarnet and ganciclovir has been shown to have enhanced activity in vitro.

Mechanism of action

Foscarnet exerts its antiviral activity by a selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases.

Absorption

Poorly absorbed after oral administration (bioavailability from 12 to 22%).

Volume of distribution

Not Available

Protein binding

14-17%

Metabolism

Not metabolized.

Route of elimination

Not Available

Half life

3.3-6.8 hours

Clearance

2.13 +/- 0.71 mL/min/kg [patients had normal renal function (CrCl > 80 mL/min]
68 +/- 8 mL/min/kg [CrCl was 50-80 mL/min]
34 +/- 9 mL/min/kg [CrCl was 25-49 mL/min]
20 +/- 4 mL/min/kg [CrCl was 10 – 24 mL/min]

Toxicity

Oral, rat LD₅₀: >2,000 mg/kg. Signs of overdose include renal impairment.

Affected organisms

Human Herpes Virus

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Hospira inc
Clinigen healthcare ltd

Packagers

Dosage forms

Form	Route	Strength
Injection, solution	Intravenous drip

Prices

Unit description	Cost	Unit
Sodium phosphonoformate powder	286.3 USD	g
Foscavir 24 mg/ml infus bottle	0.43 USD	ml
Foscarnet 24 mg/ml infus bttl	0.37 USD	ml

Patents

Not Available

Properties

State

solid

Melting point

88.06 oC

Experimental Properties

Property	Value	Source
water solubility	Complete	PhysProp
logP	-2.1	PhysProp

Predicted Properties

Property	Value	Source
water solubility	1.68e+01 g/l	ALOGPS
logP	-1.63	ALOGPS
logP	-0.83	ChemAxon Molconvert
logS	-0.88	ALOGPS
pKa	3.50	ChemAxon Molconvert
hydrogen acceptor count	5	ChemAxon Molconvert
hydrogen donor count	3	ChemAxon Molconvert
polar surface area	94.83	ChemAxon Molconvert
rotatable bond count	1	ChemAxon Molconvert
refractivity	19.07	ChemAxon Molconvert
polarizability	7.89	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D00579
PubChem Compound	3415
PubChem Substance	46507873
ChemSpider	3297
ChEBI	127780
ChEMBL	127780
Therapeutic Targets Database	DAP001383
PharmGKB	PA449706
Drug Product Database	0
RxList	http://www.rxlist.com/cgi/generic2/foscarnet.htm
Drugs.com	http://www.drugs.com/cdi/foscarnet.html
Wikipedia	http://en.wikipedia.org/wiki/Foscarnet

ATC Codes

J05AD01

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

show (100.7 KB)

MSDS

show (50.2 KB)

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. DNA polymerase Pharmacological action: yes Actions: inhibitor Organism class: viral UniProt ID: P08546 Gene: UL54 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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 Ducancelle A, Alain S, Petit F, Sanson Le Pors MJ, Mazeron MC: Development and validation of a non-radioactive DNA polymerase assay for studying cytomegalovirus resistance to foscarnet. J Virol Methods. 2007 May;141(2):212-5. Epub 2007 Jan 2. Pubmed Bonnafous P, Naesens L, Petrella S, Gautheret-Dejean A, Boutolleau D, Sougakoff W, Agut H: Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet. Antivir Ther. 2007;12(6):877-88. Pubmed Tchesnokov EP, Gilbert C, Boivin G, Gotte M: Role of helix P of the human cytomegalovirus DNA polymerase in resistance and hypersusceptibility to the antiviral drug foscarnet. J Virol. 2006 Feb;80(3):1440-50. Pubmed 2. DNA polymerase Pharmacological action: yes Actions: inhibitor Organism class: viral UniProt ID: P04293 Gene: UL30 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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 Ducancelle A, Alain S, Petit F, Sanson Le Pors MJ, Mazeron MC: Development and validation of a non-radioactive DNA polymerase assay for studying cytomegalovirus resistance to foscarnet. J Virol Methods. 2007 May;141(2):212-5. Epub 2007 Jan 2. Pubmed Bonnafous P, Naesens L, Petrella S, Gautheret-Dejean A, Boutolleau D, Sougakoff W, Agut H: Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet. Antivir Ther. 2007;12(6):877-88. Pubmed Tchesnokov EP, Gilbert C, Boivin G, Gotte M: Role of helix P of the human cytomegalovirus DNA polymerase in resistance and hypersusceptibility to the antiviral drug foscarnet. J Virol. 2006 Feb;80(3):1440-50. Pubmed

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:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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
Ducancelle A, Alain S, Petit F, Sanson Le Pors MJ, Mazeron MC: Development and validation of a non-radioactive DNA polymerase assay for studying cytomegalovirus resistance to foscarnet. J Virol Methods. 2007 May;141(2):212-5. Epub 2007 Jan 2. Pubmed
Bonnafous P, Naesens L, Petrella S, Gautheret-Dejean A, Boutolleau D, Sougakoff W, Agut H: Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet. Antivir Ther. 2007;12(6):877-88. Pubmed
Tchesnokov EP, Gilbert C, Boivin G, Gotte M: Role of helix P of the human cytomegalovirus DNA polymerase in resistance and hypersusceptibility to the antiviral drug foscarnet. J Virol. 2006 Feb;80(3):1440-50. Pubmed

2. DNA polymerase

Pharmacological action: yes
Actions: inhibitor
Organism class: viral
UniProt ID: P04293 Link_out

Gene: UL30
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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
Ducancelle A, Alain S, Petit F, Sanson Le Pors MJ, Mazeron MC: Development and validation of a non-radioactive DNA polymerase assay for studying cytomegalovirus resistance to foscarnet. J Virol Methods. 2007 May;141(2):212-5. Epub 2007 Jan 2. Pubmed
Bonnafous P, Naesens L, Petrella S, Gautheret-Dejean A, Boutolleau D, Sougakoff W, Agut H: Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet. Antivir Ther. 2007;12(6):877-88. Pubmed
Tchesnokov EP, Gilbert C, Boivin G, Gotte M: Role of helix P of the human cytomegalovirus DNA polymerase in resistance and hypersusceptibility to the antiviral drug foscarnet. J Virol. 2006 Feb;80(3):1440-50. Pubmed

Transporters
1. Solute carrier family 22 member 6 Actions: inhibitor UniProt ID: Q4U2R8 Gene: hROAT1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Wada S, Tsuda M, Sekine T, Cha SH, Kimura M, Kanai Y, Endou H: Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs. J Pharmacol Exp Ther. 2000 Sep;294(3):844-9. Pubmed 2. Monocarboxylate transporter 1 Actions: substrate Proton-linked monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate UniProt ID: P53985 Gene: SLC16A1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Tamai I, Sai Y, Ono A, Kido Y, Yabuuchi H, Takanaga H, Satoh E, Ogihara T, Amano O, Izeki S, Tsuji A: Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1. J Pharm Pharmacol. 1999 Oct;51(10):1113-21. Pubmed

Transporters

1. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out

Gene: hROAT1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Wada S, Tsuda M, Sekine T, Cha SH, Kimura M, Kanai Y, Endou H: Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs. J Pharmacol Exp Ther. 2000 Sep;294(3):844-9. Pubmed

2. Monocarboxylate transporter 1

Actions: substrate

Proton-linked monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate

UniProt ID: P53985 Link_out

Gene: SLC16A1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Tamai I, Sai Y, Ono A, Kido Y, Yabuuchi H, Takanaga H, Satoh E, Ogihara T, Amano O, Izeki S, Tsuji A: Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1. J Pharm Pharmacol. 1999 Oct;51(10):1113-21. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:04

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.