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Fosfomycin calcium (MK-0955 calcium) is a potent, blood-brain barrier penetrant phosphoenolpyruvate analog produced by Streptomyces and a synthetic broad-spectrum antibiotic with antimicrobial and bactericidal properties. Fosfomycin binds to and inactivates the enzyme enolpyruvate transferase. This leads to an irreversible blockage of the condensation of uridine diphosphate-N-acetylglucosamine with p-enolpyruvate, which is one of the first steps of bacterial cell wall synthesis.
Physicochemical Properties
| Molecular Formula | C3H5CAO4P |
| Molecular Weight | 176.12 |
| Exact Mass | 175.955 |
| Elemental Analysis | C, 20.46; H, 2.86; Ca, 22.76; O, 36.34; P, 17.59 |
| CAS # | 26016-98-8 |
| Related CAS # | Fosfomycin sodium;26016-99-9;Fosfomycin tromethamine;78964-85-9;Fosfomycin;23155-02-4 |
| PubChem CID | 93095 |
| Appearance | White to off-white solid powder |
| Boiling Point | 342.7ºC at 760 mmHg |
| Flash Point | 161ºC |
| LogP | 0.785 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 0 |
| Heavy Atom Count | 9 |
| Complexity | 127 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | [Ca+2].P([C@]1([H])[C@]([H])(C([H])([H])[H])O1)(=O)([O-])[O-] |
| InChi Key | DFBPVXQYQJJUMW-JSTPYPERSA-L |
| InChi Code | InChI=1S/2C3H7O4P.Ca/c2*1-2-3(7-2)8(4,5)6/h2*2-3H,1H3,(H2,4,5,6)/q+2/p-2/t2-,3+/m0../s1 |
| Chemical Name | calcium hydrogen ((2R,3S)-3-methyloxiran-2-yl)phosphonate hydrogen (3-methyloxiran-2-yl)phosphonate |
| Synonyms | Calcium fosfomycin; AN-8336; CS-4631; AN8336; CS4631; AN 8336; CS 4631; Phosphomycin Calcium |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Bacterial cell wall synthesis |
| ln Vitro |
The antibacterial agent found in epoxy is fosfomycin calcium. In contrast to other antibacterial agents, its mechanism of action involves impeding the initial stage of cell wall synthesis [1]. With an inhibition rate of 90%, fosfomycin calcium exhibits bactericidal activity against a range of gram-positive and gram-negative pathogens, including broad-spectrum producing β-Bacteria of lactamase and carbapenemase[1]. Research on infections of the central nervous system, soft tissues, bone, lungs, and abscesses can be conducted using fosfomycin calcium, which exhibits significant tissue penetration[2]. |
| ln Vivo | The protective effect of fosfomycin calcium (80 mg/kg; i.v.-i.v. or i.v.-p.o.) against the nephrotoxicity of double beckacin is demonstrated, and administration routes do not alter this effect[3]. |
| Enzyme Assay | Fosfomycin is a bactericidal antibiotic agent. It inhibits an enzyme-catalyzed reaction in the first step of the synthesis of the bacterial cell wall. Fosfomycin interferes with the first cytoplasmic step of bacterial cell wall biosynthesis, the formation of the peptidoglycan precursor UDP N-acetylmuramic acid (UDP-MurNAc). Specifically, the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is involved in peptidoglycan biosynthesis by catalyzing the transfer of the enolpyruvyl moiety of phosphoenolpyruvate (PEP) to the 3′-hydroxyl group of UDP-N-acetylglucosamine (UNAG). Fosfomycin covalently binds to the thiol group of a cysteine (position 115 in Escherichia coli numbering; target Cys115) in the active site of MurA and consequently inactivates it. This inhibitory action takes place at an earlier step than the action of β-lactams or glycopeptides [1]. |
| Cell Assay | Fosfomycin exerts immunomodulatory effects by altering lymphocyte, monocyte and neutrophil function. It affects the acute inflammatory cytokine response in vitro and in vivo. It suppresses production of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-1α and increases production of IL-10, while contradictory data have been published regarding IL-6. On the other hand, concentrations of TNF-α, IL-1β, and IL-6 expressed as protein and mRNA were almost identical with and without fosfomycin in healthy volunteers. Fosfomycin suppresses IL-2 production from T cells, the production of leukotriene B4 (LTB4) from neutrophils, and the expression of IL-8 mRNA by LTB4 from monocytes. Fosfomycin also exhibits an immunomodulatory effect on B-cell activation. Fosfomycin enhances neutrophil phagocytic killing of invading pathogens, even in patients on chronic hemodialysis and renal transplantation). Fosfomycin resulted in enhanced bactericidal ability of neutrophils compared to other antimicrobials. The clinical relevance of the aforementioned actions remains to be elucidated [1]. |
| Animal Protocol |
Animal Model: Fischer 344 rats[3] Dosage: 320 mg/kg Administration: Intramuscular injection, five schedules: one hour, half an hour before dibekacin, simultaneously, half an hour after, and one hour after; eleven days Result: Dibecacin (40 mg/kg)-induced reduction in polyuria, proteinuria, enzymes, and cytosine, followed by the prior treatment. |
| References |
[1]. Fosfomycin. Clin Microbiol Rev. 2016 Apr. 29(2):321-47. [2]. Fosfomycin: Pharmacological, Clinical and Future Perspectives. Antibiotics (Basel). 2017 Oct 31;6(4). pii: E24. [3]. Protective effect of fosfomycin on the experimental nephrotoxicity induced by dibekacin. J Pharmacobiodyn. 1982 Sep. 5(9):659-69. [4]. Mode of protective action of fosfomycin against dibekacin-induced nephrotoxicity in the dehydrated rats. J Pharmacobiodyn. 1982 Dec. 5(12):941-50. [5]. Reffert JL, Smith WJ. Fosfomycin for the treatment of resistant gram-negative bacterial infections. Insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2014 Aug;34(8):845-57. doi: 10.1002/phar.1434. Epub 2014 Apr 30. Review. PubMed PMID: 24782335. |
| Additional Infomation | Fosfomycin calcium is an organic molecular entity. |
Solubility Data
| Solubility (In Vitro) |
H2O : ~50 mg/mL (~283.90 mM ) DMSO : < 1 mg/mL |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.6779 mL | 28.3897 mL | 56.7795 mL | |
| 5 mM | 1.1356 mL | 5.6779 mL | 11.3559 mL | |
| 10 mM | 0.5678 mL | 2.8390 mL | 5.6779 mL |