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Showing drug card for Fosfomycin (DB00828)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:07:20
Primary Accession Number DB00828
Secondary Accession Number
  • APRD00987
Name Fosfomycin
Drug Type
  • Approved
  • Small Molecule
Description An antibiotic produced by Streptomyces fradiae. [PubChem]
Synonyms
  1. Fosfocina
  2. Fosfomycin disodium salt
  3. Fosfomycin sodium
  4. Fosfonomycin
  5. Phosphomycin
  6. Phosphonomycin
  7. phosphomycin disodium salt
Brand Names
  1. Monurol
  2. Veramina
Brand Mixtures Not Available
Chemical IUPAC Name [(2R,3S)-3-methyloxiran-2-yl]phosphonic acid
Chemical Formula C3H7O4P
Chemical Structure Structure
CAS Registry Number 23155-02-4
InChI Identifier InChI=1/C3H7O4P/c1-2-3(7-2)8(4,5)6/h2-3H,1H3,(H2,4,5,6)/t2-,3+/m0/s1/f/h4-5H
InChI Key YMDXZJFXQJVXBF-IAJFWYDIDS
KEGG Drug D04253 Link Image
KEGG Compound C06454 Link Image
PubChem Compound 446987 Link Image
PubChem Substance 8687 Link Image
ChEBI ID Not Available
PharmGKB ID PA449708 Link Image
HET ID FCN Link Image
GenBank ID Not Available
Drug ID Number [DIN] 02240335 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/fosfomycin.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/mon1275.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Fosfomycin Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 138.0590
Monoisotopic Molecular Weight 138.0082
State Solid
Melting Point 94 oC
Experimental Water Solubility 50 mg/mL (Sodium salt) Source: PhysProp
Predicted Water Solubility 4.69e+01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -1.6 Source: PhysProp
Predicted LogP -0.86 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -0.47 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES C[C@@H]1O[C@@H]1P(O)(O)=O
Canonical SMILES CC1OC1P(O)(O)=O
Drug Category
  • Anti-Bacterial Agents
ATC Codes
AHFS Codes
  • 08:36.00
Indication For the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis.
Pharmacology 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%
Toxicity LD50>5 g/kg (rats). Side effects may include diarrhea
Protein Binding 0% (not bound to plasma proteins)
Biotransformation No transformation, excreted unchanged
Half Life 5.7 (± 2.8) hours. The elimination half-life is 40 hours in anuric patients undergoing hemodialysis.
Dosage Forms
Form Route
Powder Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions
  • Food decreases Cmax slightly.
  • Take without regard to meals.
Pathways Not Available
General References
  1. Wikipedia Link Image
  2. RxList Link Image
  3. PDRhealth Link Image
Organisms Affected
  • Enteric bacteria and other eubacteria
Targets
  1. UDP-N-acetylglucosamine 1-carboxyvinyltransferase
Drug Target 1 [top]
Target 1 ID 520
Target 1 Name UDP-N-acetylglucosamine 1-carboxyvinyltransferase
Target 1 Synonyms
  1. EC 2.5.1.7
  2. EPT
  3. Enoylpyruvate transferase
  4. UDP-N-acetylglucosamine enolpyruvyl transferase
Target 1 Gene Name murA
Target 1 Protein Sequence >UDP-N-acetylglucosamine 1-carboxyvinyltransferase 
MDKFRVQGPTKLQGEVTISGAKNAALPILFAALLAEEPVEIQNVPKLKDVDTSMKLLSQL
GAKVERNGSVHIDARDVNVFCAPYDLVKTMRASIWALGPLVARFGQGQVSLPGGCTIGAR
PVDLHISGLEQLGATIKLEEGYVKASVDGRLKGAHIVMDKVSVGATVTIMCAATLAEGTT
IIENAAREPEIVDTANFLITLGAKISGQGTDRIVIEGVERLGGGVYRVLPDRIETGTFLV
AAAISRGKIICRNAQPDTLDAVLAKLRDAGADIEVGEDWISLDMHGKRPKAVNVRTAPHP
AFPTDMQAQFTLLNLVAEGTGFITETVFENRFMHVPELSRMGAHAEIESNTVICHGVEKL
SGAQVMATDLRASASLVLAGCIAEGTTVVDRIYHIDRGYERIEDKLRALGANIERVKGE
Target 1 Number of Residues 425
Target 1 Molecular Weight 44818
Target 1 Theoretical pI 6.07
Target 1 GO Classification
Function
catalytic activity
transferase activity
Process
physiological process
metabolism
nitrogen compound metabolism
amine metabolism
amino sugar metabolism
UDP-N-acetylgalactosamine metabolism
UDP-N-acetylgalactosamine biosynthesis
Component
Not Available
Target 1 General Function Cell wall/membrane/envelope biogenesis
Target 1 Specific Function Cell wall formation. Adds enolpyruvyl to UDP-N- acetylglucosamine. Target for the antibiotic phosphomycin
Target 1 Pathways
Name SMPDB Link KEGG Link
Aminosugars metabolism map00530 Link Image
Target 1 Reactions
  • phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Essential
Target 1 GenBank ID Protein 146902 Link Image
Target 1 UniProtKB/Swiss-Prot ID P0A749 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name MURA_ECOLI Link Image
Target 1 PDB ID 1UAE Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Cytoplasm (Probable)
Target 1 Gene Sequence >1260 bp 
ATGGATAAATTTCGTGTTCAGGGGCCAACGAAGCTCCAGGGCGAAGTCACAATTTCCGGC
GCTAAAAATGCTGCTCTGCCTATCCTTTTTGCCGCACTACTGGCGGAAGAACCGGTAGAG
ATCCAGAACGTCCCGAAACTGAAAGACGTCGATACATCAATGAAGCTGCTAAGCCAGCTG
GGTGCGAAAGTAGAACGTAATGGTTCTGTGCATATTGATGCCCGCGACGTTAATGTATTC
TGCGCACCTTACGATCTGGTTAAAACCATGCGTGCTTCTATCTGGGCGCTGGGGCCGCTG
GTAGCGCGCTTTGGTCAGGGGCAAGTTTCACTACCTGGCGGTTGTACGATCGGTGCGCGT
CCGGTTGATCTACACATTTCTGGCCTCGAACAATTAGGCGCGACCATCAAACTGGAAGAA
GGTTACGTTAAAGCTTCCGTCGATGGTCGTTTGAAAGGTGCACATATCGTGATGGATAAA
GTCAGCGTTGGCGCAACGGTGACCATCATGTGTGCTGCAACCCTGGCGGAAGGCACCACG
ATTATTGAAAACGCAGCGCGTGAACCGGAAATCGTCGATACCGCGAACTTCCTGATTACG
CTGGGTGCGAAAATTAGCGGTCAGGGCACCGATCGTATCGTCATCGAAGGTGTGGAACGT
TTAGGCGGCGGTGTCTATCGCGTTCTGCCGGATCGTATCGAAACCGGTACTTTCCTGGTG
GCGGCGGCGATTTCTCGCGGCAAAATTATCTGCCGTAACGCGCAGCCAGATACTCTCGAC
GCCGTGCTGGCGAAACTGCGTGACGCTGGAGCGGACATCGAAGTCGGCGAAGACTGGATT
AGCCTGGATATGCATGGCAAACGTCCGAAGGCTGTTAACGTACGTACCGCGCCGCATCCG
GCATTCCCGACCGATATGCAGGCCCAGTTCACGCTGTTGAACCTGGTGGCAGAAGGGACC
GGGTTTATCACCGAAACGGTCTTTGAAAACCGCTTTATGCATGTGCCAGAGCTGAGCCGT
ATGGGCGCGCACGCCGAAATCGAAAGCAATACCGTTATTTGTCACGGTGTTGAAAAACTT
TCTGGCGCACAGGTTATGGCAACCGATCTGCGTGCATCAGCAAGCCTGGTGCTGGCTGGC
TGTATTGCGGAAGGGACGACGGTGGTTGATCGTATTTATCACATCGATCGTGGCTACGAA
CGCATTGAAGACAAACTGCGCGCTTTAGGTGCAAATATTGAGCGTGTGAAAGGCGAATAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID Not Available
Target 1 GenAtlas ID Not Available
Target 1 HGNC ID Not Available
Target 1 Chromosome Location Not Available
Target 1 Locus Not Available
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Horii T, Kimura T, Sato K, Shibayama K, Ohta M: Emergence of fosfomycin-resistant isolates of Shiga-like toxin-producing Escherichia coli O26. Antimicrob Agents Chemother. 1999 Apr;43(4):789-93. [PubMed Link Image]
  2. Marquardt JL, Siegele DA, Kolter R, Walsh CT: Cloning and sequencing of Escherichia coli murZ and purification of its product, a UDP-N-acetylglucosamine enolpyruvyl transferase. J Bacteriol. 1992 Sep;174(17):5748-52. [PubMed Link Image]
  3. Skarzynski T, Mistry A, Wonacott A, Hutchinson SE, Kelly VA, Duncan K: Structure of UDP-N-acetylglucosamine enolpyruvyl transferase, an enzyme essential for the synthesis of bacterial peptidoglycan, complexed with substrate UDP-N-acetylglucosamine and the drug fosfomycin. Structure. 1996 Dec 15;4(12):1465-74. [PubMed Link Image]
  4. Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-74. [PubMed Link Image]
  5. Skarzynski T, Kim DH, Lees WJ, Walsh CT, Duncan K: Stereochemical course of enzymatic enolpyruvyl transfer and catalytic conformation of the active site revealed by the crystal structure of the fluorinated analogue of the reaction tetrahedral intermediate bound to the active site of the C115A mutant of MurA. Biochemistry. 1998 Feb 24;37(8):2572-7. [PubMed Link Image]
Target 1 Drug References
  1. 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 Link Image]
  2. 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 Link Image]
  3. 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 Link Image]
  4. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
  5. 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 Link Image]

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.