|Accession Number||DB00828 (APRD00987)|
An antibiotic produced by Streptomyces fradiae. [PubChem]
|Approved Prescription Products|
|Approved Generic Prescription Products||Not Available|
|Approved Over the Counter Products||Not Available|
|Unapproved/Other Products||Not Available|
|Brand mixtures||Not Available|
|Weight||Average: 138.059 |
For the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis.
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.
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|
0% (not bound to plasma proteins)
No transformation, excreted unchanged
|Route of elimination|
Fosfomycin is excreted unchanged in both urine and feces.
5.7 (± 2.8) hours. The elimination half-life is 40 hours in anuric patients undergoing hemodialysis.
LD50>5 g/kg (rats). Side effects may include diarrhea
|Pharmacogenomic Effects/ADRs||Not Available|
Graziano Castaldi, Claudio Giordano, "Process for the preparation of intermediates for the synthesis of fosfomycin." U.S. Patent US4937367, issued March, 1972.US4937367
|General References||Not Available|
|ATC Codes||J01XX01 — Fosfomycin|
|PDB Entries||Not Available|
|FDA label||Download (267 KB)|
|MSDS||Download (61.1 KB)|
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
|Predicted ADMET features|
|Mass Spec (NIST)||Not Available|
|Description||This compound belongs to the class of chemical entities known as organic phosphonic acids. These are organic compounds containing phosphonic acid.|
|Super Class||Organic compounds|
|Class||Organic acids and derivatives|
|Sub Class||Organic phosphonic acids and derivatives|
|Direct Parent||Organic phosphonic acids|
|Alternative Parents||Oxacyclic compounds / Epoxides / Organopnictogen compounds / Organophosphorus compounds / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives|
|Substituents||Organophosphonic acid / Oxacycle / Organoheterocyclic compound / Oxirane / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Organophosphorus compound / Organooxygen compound|
|Molecular Framework||Aliphatic heteromonocyclic compounds|
|External Descriptors||epoxide, phosphonic acids (CHEBI:28915 ) / Aliphatic compounds (C06454 )|
- Escherichia coli (strain K12)
- Pharmacological action
- General Function:
- Udp-n-acetylglucosamine 1-carboxyvinyltransferase activity
- Specific Function:
- Cell wall formation. Adds enolpyruvyl to UDP-N-acetylglucosamine. Target for the antibiotic fosfomycin.
- Gene Name:
- Uniprot ID:
- Molecular Weight:
- 44817.24 Da
- 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 ]
- 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 ]
- 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:8664284 ]
- 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:15531591 ]
- 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:12562791 ]
- 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:7608103 ]
- 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:10529188 ]