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Identification
Name Fosfomycin
Accession Number DB00828 (APRD00987)
Type small molecule
Groups approved
Description

An antibiotic produced by Streptomyces fradiae. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Fosfocina
  • Fosfomycin disodium salt
  • Fosfomycin sodium
  • Fosfonomycin
  • Phosphomycin
  • phosphomycin disodium salt
  • Phosphonomycin
Brand names
  • Monurol
  • Veramina
Brand name mixtures Not Available
Categories
  • Anti-Bacterial Agents
CAS number 23155-02-4
Weight Average: 138.059
Monoisotopic: 138.008195224
Chemical Formula C3H7O4P
InChI Key InChIKey=YMDXZJFXQJVXBF-STHAYSLISA-N
InChI
InChI=1S/C3H7O4P/c1-2-3(7-2)8(4,5)6/h2-3H,1H3,(H2,4,5,6)/t2-,3+/m0/s1
Plain Text
IUPAC Name
[(2R,3S)-3-methyloxiran-2-yl]phosphonic acid
SMILES
C[C@@H]1O[C@@H]1P(O)(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phosphonic Acids and Derivatives
Substructures
  • Hydroxy Compounds
  • Phosphonic Acids and Derivatives
  • Ethers
  • Heterocyclic compounds
  • Phosphinic Acids and Derivatives
  • Epoxides
Pharmacology
Indication For the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis.
Pharmacodynamics Fosfomycin is a broad spectrum antibiotic that concentrates in kidney and bladder and is used to treat uncomplicated urinary tract infections. Fosfomycin also reduces nephrotoxicity and ototoxicity of platinum-containing anti-tumor agents.
Mechanism of action Fosfomycin is a phosphoenolpyruvate analogue produced by Streptomyces that irreversibly inhibits enolpyruvate transferase (MurA), which prevents the formation of N-acetylmuramic acid, an essential element of the peptidoglycan cell wall.
Absorption Fosfomycin tromethamine is rapidly absorbed following oral administration and converted to fosfomycin. Oral bioavailability under fasting conditions is 37%. When given with food, oral bioavailability is reduced to 30%
Volume of distribution
  • 136.1 ±44.1 L
Protein binding 0% (not bound to plasma proteins)
Metabolism

No transformation, excreted unchanged
Route of elimination Fosfomycin is excreted unchanged in both urine and feces.
Half life 5.7 (± 2.8) hours. The elimination half-life is 40 hours in anuric patients undergoing hemodialysis.
Clearance
  • 16.9 +/- 3.5 L/hr
Toxicity LD50>5 g/kg (rats). Side effects may include diarrhea
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Zambon spa italy
Packagers
Dosage forms
Form Route Strength
Powder Oral
Prices
Unit description Cost Unit
Monurol 3 gm Packets 50.87 USD packet
Monurol 3 gm sachet 47.07 USD each
Viramune 200 mg tablet 9.48 USD tablet
Patents Not Available
Properties
State solid
Melting point 94 oC
Experimental Properties
Property Value Source
water solubility 50 mg/mL (Sodium salt) PhysProp
logP -1.6 PhysProp
Predicted Properties
Property Value Source
water solubility 4.69e+01 g/l ALOGPS
logP -0.86 ALOGPS
logP -0.74 ChemAxon Molconvert
logS -0.47 ALOGPS
pKa 7.82 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 70.06 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 25.87 ChemAxon Molconvert
polarizability 10.81 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D04253 Link_out
KEGG Compound C06454 Link_out
PubChem Compound 446987 Link_out
PubChem Substance 46506665 Link_out
ChemSpider 394204 Link_out
Therapeutic Targets Database DAP000767 Link_out
PharmGKB PA449708 Link_out
HET FCN Link_out
Drug Product Database 2240335 Link_out
RxList http://www.rxlist.com/cgi/generic2/fosfomycin.htm Link_out
Drugs.com http://www.drugs.com/cdi/fosfomycin.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/mon1275.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Fosfomycin Link_out
ATC Codes
  • J01XX01
AHFS Codes
  • 08:36.00
PDB Entries Not Available
FDA label show (266.8 KB)
MSDS show (61.1 KB)
Interactions
Drug Interactions
Drug Interaction
Food Interactions
  • Food decreases Cmax slightly.
  • Take without regard to meals.
Targets

1. UDP-N-acetylglucosamine 1-carboxyvinyltransferase

Pharmacological action: yes
Actions: inhibitor

Cell wall formation. Adds enolpyruvyl to UDP-N- acetylglucosamine. Target for the antibiotic phosphomycin

Organism class: bacterial
UniProt ID: P0A749 Link_out
Gene: murA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Kim DH, Lees WJ, Kempsell KE, Lane WS, Duncan K, Walsh CT: Characterization of a Cys115 to Asp substitution in the Escherichia coli cell wall biosynthetic enzyme UDP-GlcNAc enolpyruvyl transferase (MurA) that confers resistance to inactivation by the antibiotic fosfomycin. Biochemistry. 1996 Apr 16;35(15):4923-8. Pubmed
  4. Eschenburg S, Priestman M, Schonbrunn E: Evidence that the fosfomycin target Cys115 in UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is essential for product release. J Biol Chem. 2005 Feb 4;280(5):3757-63. Epub 2004 Nov 5. Pubmed
  5. McCoy AJ, Sandlin RC, Maurelli AT: In vitro and in vivo functional activity of Chlamydia MurA, a UDP-N-acetylglucosamine enolpyruvyl transferase involved in peptidoglycan synthesis and fosfomycin resistance. J Bacteriol. 2003 Feb;185(4):1218-28. Pubmed
  6. Brown ED, Vivas EI, Walsh CT, Kolter R: MurA (MurZ), the enzyme that catalyzes the first committed step in peptidoglycan biosynthesis, is essential in Escherichia coli. J Bacteriol. 1995 Jul;177(14):4194-7. Pubmed
  7. Samland AK, Amrhein N, Macheroux P: Lysine 22 in UDP-N-acetylglucosamine enolpyruvyl transferase from Enterobacter cloacae is crucial for enzymatic activity and the formation of covalent adducts with the substrate phosphoenolpyruvate and the antibiotic fosfomycin. Biochemistry. 1999 Oct 5;38(40):13162-9. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:43

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.