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Identification
NameFosfomycin
Accession NumberDB00828  (APRD00987)
TypeSmall Molecule
GroupsApproved
Description

An antibiotic produced by Streptomyces fradiae. [PubChem]

Structure
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Synonyms
(-)-(1R,2S)-(1,2-Epoxypropyl)phosphonic acid
(1R,2S)-Epoxypropylphosphonic acid
(2R-cis)-(3-Methyloxiranyl)phosphonic acid
1R-cis-(1,2-Epoxypropyl)phosphonic acid
cis-(1R,2S)-Epoxypropylphosphonic acid
FCM
Fosfocina
Fosfomicina
FOSFOMYCIN
Fosfomycine
Fosfomycinum
L-cis-1,2-Epoxypropylphosphonic acid
Phosphomycin
Phosphonemycin
Phosphonomycin
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Monurolpowder3 g/1oralForest Laboratories1996-12-19Not applicableUs
Monurolpowder3 goralPaladin Labs Inc1999-09-15Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
VeraminaRoux-Ocefa
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Fosfomycin calcium monohydrate
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  • InChI Key: MSHCINMVQZDXTG-JSTPYPERSA-N
  • Monoisotopic Mass: 195.981351065
  • Average Mass: 196.152
DBSALT000780
Fosfomycin disodium
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  • InChI Key: QZIQJIKUVJMTDG-JSTPYPERSA-L
  • Monoisotopic Mass: 181.97208451
  • Average Mass: 182.0227
DBSALT000454
Fosfomycin tromethamine
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  • InChI Key: QZJIMDIBFFHQDW-LMLSDSMGSA-N
  • Monoisotopic Mass: 259.082088447
  • Average Mass: 259.1941
DBSALT000781
Categories
UNII2N81MY12TE
CAS number23155-02-4
WeightAverage: 138.059
Monoisotopic: 138.008195224
Chemical FormulaC3H7O4P
InChI KeyInChIKey=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
IUPAC Name
[(2R,3S)-3-methyloxiran-2-yl]phosphonic acid
SMILES
C[C@@H]1O[C@@H]1P(O)(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as organic phosphonic acids. These are organic compounds containing phosphonic acid.
KingdomOrganic compounds
Super ClassOrganophosphorus compounds
ClassOrganic phosphonic acids and derivatives
Sub ClassOrganic phosphonic acids
Direct ParentOrganic phosphonic acids
Alternative Parents
Substituents
  • Organophosphonic acid
  • Oxacycle
  • Organoheterocyclic compound
  • Oxirane
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis.
PharmacodynamicsFosfomycin 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 actionFosfomycin 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.
Related Articles
AbsorptionFosfomycin 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 binding0% (not bound to plasma proteins)
Metabolism

No transformation, excreted unchanged

Route of eliminationFosfomycin is excreted unchanged in both urine and feces.
Half life5.7 (± 2.8) hours. The elimination half-life is 40 hours in anuric patients undergoing hemodialysis.
Clearance
  • 16.9 +/- 3.5 L/hr
ToxicityLD50>5 g/kg (rats). Side effects may include diarrhea
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.5
Blood Brain Barrier+0.9382
Caco-2 permeable-0.6652
P-glycoprotein substrateNon-substrate0.7234
P-glycoprotein inhibitor INon-inhibitor0.8938
P-glycoprotein inhibitor IINon-inhibitor0.9878
Renal organic cation transporterNon-inhibitor0.9505
CYP450 2C9 substrateNon-substrate0.7514
CYP450 2D6 substrateNon-substrate0.8332
CYP450 3A4 substrateNon-substrate0.6513
CYP450 1A2 substrateNon-inhibitor0.8492
CYP450 2C9 inhibitorNon-inhibitor0.8551
CYP450 2D6 inhibitorNon-inhibitor0.9202
CYP450 2C19 inhibitorNon-inhibitor0.8016
CYP450 3A4 inhibitorNon-inhibitor0.9624
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.944
Ames testNon AMES toxic0.6575
CarcinogenicityNon-carcinogens0.6059
BiodegradationNot ready biodegradable0.894
Rat acute toxicity2.5802 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9456
hERG inhibition (predictor II)Non-inhibitor0.9491
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Zambon spa italy
Packagers
Dosage forms
FormRouteStrength
Powderoral3 g/1
Powderoral3 g
Prices
Unit descriptionCostUnit
Monurol 3 gm Packets50.87USD packet
Monurol 3 gm sachet47.07USD each
Viramune 200 mg tablet9.48USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point94 °CPhysProp
water solubility50 mg/mL (Sodium salt)Not Available
logP-1.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility46.9 mg/mLALOGPS
logP-0.86ALOGPS
logP-0.74ChemAxon
logS-0.47ALOGPS
pKa (Strongest Acidic)1.25ChemAxon
pKa (Strongest Basic)-4.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area70.06 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity25.87 m3·mol-1ChemAxon
Polarizability10.8 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-03di-2980000000-005d5b96a1e9219362d0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
References
Synthesis Reference

Graziano Castaldi, Claudio Giordano, “Process for the preparation of intermediates for the synthesis of fosfomycin.” U.S. Patent US4937367, issued March, 1972.

US4937367
General ReferencesNot Available
External Links
ATC CodesJ01XX01
AHFS Codes
  • 08:36.00
PDB EntriesNot Available
FDA labelDownload (267 KB)
MSDSDownload (61.1 KB)
Interactions
Drug Interactions
Drug
Picosulfuric acidThe therapeutic efficacy of Sodium picosulfate can be decreased when used in combination with Fosfomycin.
Food Interactions
  • Food decreases Cmax slightly.
  • Take without regard to meals.

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
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:
murA
Uniprot ID:
P0A749
Molecular Weight:
44817.24 Da
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:17139284 ]
  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:17016423 ]
  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:8664284 ]
  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:15531591 ]
  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:12562791 ]
  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:7608103 ]
  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:10529188 ]
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12