Fosfomycin sodium
(Synonyms: 磷霉素钠; MK-0955 sodium) 目录号 : GC60854
Fosfomycin sodium是一种磷酸烯醇丙酮酸（PEP）类似物，作为强效口服抗生素，可通过抑制大肠杆菌MurA酶发挥抗菌作用，IC50值为8.8μmol/L。
Cas No.:26016-99-9
Sample solution is provided at 25 µL, 10mM.
Fosfomycin sodium, a phosphoenolpyruvate (PEP) analog, is a powerful and orally active antibiotic that inhibits Escherichia coli MurA Enzyme with IC50 value of 8.8μmol/L[1]. Fosfomycin sodium covalently modifies the thiol of a cysteine (position 115 in Escherichia coli numbering; target Cys115) in the active site of MurA and thereby inactivates the enzyme[2]. Fosfomycin sodium has been employed in antibacterial and immunoregulatory assays[3].
In vitro, Fosfomycin sodium was active against 88.6% of the extended spectrum ß-lactamases (ESBLs)-producing E. coli ESBL strains and the MIC values (16h) for most of the strains were ≤16mg/L. The MIC50 and MIC90 were 1 and 32mg/L, respectively, for 16h[4]. Treatment of HEK293 human embryonic kidney cells with Fosfomycin sodium for 24h significantly inhibited cell viability with the IC50 values of 41.4μg/ml[5]. Fosfomycin sodium treatment (200μg/ml, 48h) significantly inhibited proliferation of Human peripheral blood mononuclear cells, accompanied by the reduced IL-2 levels[6].
In vivo, Fosfomycin sodium at a dose of 320mg/kg/day (12 days, intramuscular injection) has a significant protective effect on experimental nephrotoxicity induced by dibekacin (40mg/kg/day, intramuscular injection) in male Fischer 344 rats, resulting in improvement of renal histopathology and ultrastructure, and reduction of blood urea nitrogen and creatinine levels in rats[7]. Intravenous administration of Fosfomycin sodium at a dose of 120mg/kg/day significantly improved acute renal failure induced by 30mg/kg dibekacin (Intravenous injection), inhibited myeloid formation and protected lysosomal membrane integrity in Male Wistar SPF rats[8].
References:
[1] Baum E Z, Montenegro D A, Licata L, et al. Identification and characterization of new inhibitors of the Escherichia coli MurA enzyme[J]. Antimicrobial agents and chemotherapy, 2001, 45(11): 3182-3188.
[2] Falagas M E, Vouloumanou E K, Samonis G, et al. Fosfomycin[J]. Clinical microbiology reviews, 2016, 29(2): 321-347.
[3] Silver L L. Fosfomycin: mechanism and resistance[J]. Cold Spring Harbor perspectives in medicine, 2017, 7(2): a025262.
[4] Aprile A, Scalia G, Stefani S, et al. In vitro fosfomycin study on concordance of susceptibility testing methods against ESBL and carbapenem-resistant Enterobacteriaceae[J]. Journal of Global Antimicrobial Resistance, 2020, 23: 286-289.
[5]Khazaal M T, Faraag A H I, El-Hendawy H H. In vitro and in silico studies of enterobactin-inspired Ciprofloxacin and Fosfomycin first generation conjugates on the antibiotic resistant E. coli OQ866153[J]. BMC microbiology, 2024, 24(1): 95.
[6] Morikawa K, Oseko F, Morikawa S, et al. Immunosuppressive activity of fosfomycin on human T-lymphocyte function in vitro[J]. Antimicrobial agents and chemotherapy, 1993, 37(12): 2684-2687.
[7] INOUYE S, NIIZATO T, TAKEDA U, et al. Protective effect of fosfomycin on the experimental nephrotoxicity induced by dibekacin[J]. Journal of pharmacobio-dynamics, 1982, 5(9): 659-669.
[8] INOUYE S, NIIZATO T, KOMIYA I, et al. Mode of protective action of fosfomycin against dibekacin-induced nephrotoxicity in the dehydrated rats[J]. Journal of pharmacobio-dynamics, 1982, 5(12): 941-950.
Fosfomycin sodium是一种磷酸烯醇丙酮酸（PEP）类似物，作为强效口服抗生素，可通过抑制大肠杆菌MurA酶发挥抗菌作用，IC50值为8.8μmol/L[1]。Fosfomycin sodium通过共价修饰MurA酶活性位点的半胱氨酸残基（在大肠杆菌中为Cys115位点）的巯基，从而使MurA酶失活[2]。Fosfomycin sodium已被广泛应用于抗菌试验和免疫调节研究[3]。
在体外，Fosfomycin sodium在对产超广谱β-内酰胺酶（ESBL）的大肠杆菌表现出显著的抗菌活性，抑制率达88.6%，对大多数菌株在16小时内的MIC ≤16mg/L，其中MIC50和MIC90分别为1mg/L和32mg/L[4]。Fosfomycin sodium处理24小时后显著抑制人胚胎肾细胞HEK293的细胞活性，IC50值为41.4μg/ml[5]。Fosfomycin sodium处理（200μg/ml，48小时）能显著抑制人外周血单个核细胞的增殖，并降低IL-2的分泌水平[6]。
在体内，Fosfomycin sodium处理（320mg/kg/day，肌肉注射，12天）对地贝卡星（40mg/kg/day，肌肉注射）诱导的雄性Fischer 344大鼠肾毒性具有显著保护作用，可改善肾脏组织病理学变化和超微结构，并降低血尿素氮和肌酐水平[7]。在雄性Wistar SPF大鼠中，静脉注射Fosfomycin sodium（120mg/kg/day）能有效缓解地贝卡星（30mg/kg，静脉注射）引起的急性肾衰竭，抑制髓样结构形成并保护溶酶体膜完整性[7]。
| Cell experiment [1]: | |
Cell lines | Human peripheral blood mononuclear cells |
Preparation Method | Human peripheral blood mononuclear cells (PBMCs) (105cells/well) were incubated with and without S-(2-Aminoethyl) isothiuronium bromide hydrobromide for 3 days. During the final 18h of culture, PBMCs were pulsed with 1μCi [3H]thymidine/well, and harvested using a multi-well cell harvester. Surface activation antigens were looked for on the cells at direct immunofluorescence analysis on fluorescein isothiocyanate-conjugated monoclonal antibodies after 4 days of incubation in the presence or absence of reagents. Flow cytometry was performed to detect cell surface immunofluorescence. PBMCs were adjusted to 106cells/ml (1ml/well) and then cultured in 24-well plate wells with pokeweed mitogen (1:50 dilution) in the presence or absence of Fosfomycin sodium (1.6, 8, 50 and 200μg/ml), FK506 (0.001μg/ml) or Cs-A (0.1μg/ml), respectively, for 48h at 37℃ in a 5% CO2 incubator. Supernatants were harvested after centrifugation and stored at -20°C until assayed. |
Reaction Conditions | 1.6, 8, 50 and 200μg/ml; 48h |
Applications | Fosfomycin sodium (200μg/ml) significantly inhibited proliferation of PBMCs and strongly suppressed IL-2 production. |
| Animal experiment [2]: | |
Animal models | Male Fischer 344 rats |
Preparation Method | Nephrotoxicity studies were performed in 8-week-old male Fischer 344 rats with a body weight ranging between 270g and 320g. Six rats were employed per group in preliminary investigations, and 12 rats in regular protective effect measurement. All rats were randomly allocated and housed singly with ad libitum access to standard rat chow and tap water. The day before the start day (day 0), day 2, 5, 8, 11, all the animals were individually caged during the night in metabolic cages and 17-h urine was collected between 5 PM and 10 AM and kept at 4℃ until analysis. Dibekacin was administered intramuscularly once daily at a dose of 40mg/kg. Fosfomycin sodium was administered intramuscularly at a dose of 320mg/kg/day in five independent schedules of dose separation: 1h earlier than dibekacin, 0.5h earlier, concomitantly, 0.5h later and lh later. Daily urine samples were analyzed for urinary protein, N-acetyl-β-D-glucosaminidase and nucleated cells. |
Dosage form | 320mg/kg/day for 12 days; i.m. |
Applications | Fosfomycin sodium had a significant protective effect against dibekacin induced experimental nephrotoxicity of rats, resulting in histopathological and ultrastructural improvement of renal end tubules and reduction of blood urea nitrogen and creatinine levels in rats. |
References: | |
| Cas No. | 26016-99-9 | SDF | |
| 别名 | 磷霉素钠; MK-0955 sodium | ||
| Canonical SMILES | C[C@@H]1O[C@@H]1P(O[Na])(O[Na])=O | ||
| 分子式 | C3H5Na2O4P | 分子量 | 182.02 |
| 溶解度 | Water: 125 mg/mL (686.74 mM) | 储存条件 | Store at 4°C, away from moisture |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 5.4939 mL | 27.4695 mL | 54.939 mL |
| 5 mM | 1.0988 mL | 5.4939 mL | 10.9878 mL |
| 10 mM | 0.5494 mL | 2.747 mL | 5.4939 mL |
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动物平均体重 | g | |
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动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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Quality Control & SDS
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- Biological Activity: 720U/mg
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