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Purity: ≥98%
Cefoselis (also known as FK 037 Sulfate) is a widely used beta-lactam antibiotic of the cephalosporin class. Cefoselis inhibits GABA-induced currents in a concentration-dependent manner with IC50 of 185 mM. Cefoselis possesses a superior antistaphylococcal activity on MSSA isolates to both other compounds being however equal active to Cefepime and Cefpirome on multiresistant enterobacteriaceae. Cefoselis is dose-dependently appeared in brain extracellular fluid in proportion to its blood level. Cefoselis, a new parenteral cephalosporin, is active against clinical isolates of both gram-positive and gram-negative aerobic bacteria.
| Targets |
β-lactam
Bacterial Penicillin-Binding Proteins (PBPs) (MIC values: Escherichia coli = 0.015-0.12 μg/mL; Klebsiella pneumoniae = 0.03-0.25 μg/mL; Staphylococcus aureus = 0.25-1 μg/mL) [2][3] |
|---|---|
| ln Vitro |
Cefoselis inhibits GABA-induced currents in a concentration-dependent manner with IC50 of 185 mM. Cefoselis possesses a superior antistaphylococcal activity on MSSA isolates to both other compounds being however equal active to Cefepime and Cefpirome on multiresistant enterobacteriaceae. Cefoselis is dose-dependently appeared in brain extracellular fluid in proportion to its blood level. Cefoselis, a new parenteral cephalosporin, is active against clinical isolates of both gram-positive and gram-negative aerobic bacteria.
Cefoselis Sulfate (FK-037) exhibits broad-spectrum antibacterial activity against Gram-negative and Gram-positive bacteria. For Gram-negative bacteria: it inhibited Escherichia coli (including ESBL-producing strains) with MIC50 = 0.03 μg/mL, MIC90 = 0.06 μg/mL; Klebsiella pneumoniae with MIC50 = 0.06 μg/mL, MIC90 = 0.12 μg/mL; Pseudomonas aeruginosa with MIC50 = 1 μg/mL, MIC90 = 2 μg/mL [2][3] - For Gram-positive bacteria: it suppressed methicillin-susceptible Staphylococcus aureus (MSSA) with MIC50 = 0.5 μg/mL, MIC90 = 1 μg/mL; Streptococcus pneumoniae with MIC50 = 0.03 μg/mL, MIC90 = 0.06 μg/mL; Enterococcus faecalis with MIC50 = 2 μg/mL, MIC90 = 4 μg/mL [3] - It showed bactericidal activity: time-kill curve assays demonstrated that at 2×MIC, it reduced viable counts of Escherichia coli by ≥3 log10 CFU/mL within 6 hours and Pseudomonas aeruginosa by ≥3 log10 CFU/mL within 8 hours [3] - It is stable to most β-lactamases (ESBLs, AmpC β-lactamases) but susceptible to metallo-β-lactamases (MBLs) [2] - In rat cortical neurons, Cefoselis Sulfate (FK-037) (100-1000 μg/mL) induced concentration-dependent glutamate release: 500 μg/mL increased glutamate levels by ~2.8-fold compared to control, which is associated with seizure induction [1] - No significant cytotoxicity to human epithelial cells (HEp-2) at concentrations up to 200 μg/mL [3] |
| ln Vivo |
Cefoselis elicits a massive elevation of extracellular glutamate concentration in normal rats. Cefoselis (50 mg/animal)-induced convulsions are prevented by pretreatment with 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), diazepam and phenobarbital (ED(50) values (mg/kg) of 0.78, 1.59 and 33.0, respectively), but not by carbamazepine or phenytoin.
In rats, intravenous administration of Cefoselis Sulfate (FK-037) (100 mg/kg, 200 mg/kg) easily penetrated the blood-brain barrier (BBB), with a cerebrospinal fluid (CSF)/plasma concentration ratio of 0.25 (100 mg/kg) and 0.32 (200 mg/kg) at 1 hour post-administration [1] - It induced dose-dependent seizures in rats: intravenous injection of 200 mg/kg caused generalized seizures in 80% of rats, while 100 mg/kg induced mild seizures in 30% of rats. The seizure activity was correlated with increased glutamate levels in the cerebral cortex [1] |
| Enzyme Assay |
Bacterial PBP binding assay: Purified PBPs (PBP1a, PBP2, PBP3) from Escherichia coli and Staphylococcus aureus were incubated with Cefoselis Sulfate (FK-037) (0.01-20 μg/mL) and radiolabeled penicillin G at 37°C for 30 minutes. SDS-PAGE electrophoresis and autoradiography were used to quantify PBP binding inhibition, confirming high affinity for PBP2 and PBP3 [3]
- MIC determination assay: Clinical bacterial isolates were inoculated into Mueller-Hinton broth containing serial dilutions of Cefoselis Sulfate (FK-037) (0.001-128 μg/mL) and incubated at 37°C for 18-24 hours. The lowest concentration inhibiting visible bacterial growth was defined as MIC [2][3] - β-lactamase stability assay: Cefoselis Sulfate (FK-037) (10 μg/mL) was incubated with purified β-lactamases (ESBLs, AmpC, MBLs) at 37°C for 1 hour. Residual antibacterial activity was measured by agar diffusion assay, with inhibition zone diameter used to evaluate stability [2] |
| Cell Assay |
Time-kill curve assay: Bacterial suspensions (10⁶ CFU/mL) were incubated with Cefoselis Sulfate (FK-037) at 0.5×MIC, 1×MIC, 2×MIC, and 4×MIC at 37°C. Aliquots were sampled at 0, 2, 4, 6, 8, and 24 hours, serially diluted, and plated on agar plates. Colonies were counted after 24 hours to determine viable bacterial counts [3]
- Neuronal glutamate release assay: Rat cortical neurons were cultured in 24-well plates for 7 days, then treated with Cefoselis Sulfate (FK-037) (100-1000 μg/mL) for 30 minutes. Culture supernatants were collected, and glutamate levels were measured by fluorometric assay using glutamate dehydrogenase [1] - Cytotoxicity assay: Human HEp-2 cells were seeded in 96-well plates and treated with Cefoselis Sulfate (FK-037) (0.1-200 μg/mL) for 24 hours. MTT reagent was added, and absorbance at 570 nm was measured to evaluate cell viability [3] |
| Animal Protocol |
50 mg/animal
Rats Rat BBB penetration and seizure model: Sprague-Dawley rats were randomly divided into control and Cefoselis Sulfate (FK-037) treatment groups (100 mg/kg, 200 mg/kg). The drug was dissolved in normal saline and administered via intravenous injection. At 1 hour post-administration, rats were anesthetized to collect blood and cerebrospinal fluid for drug concentration detection (HPLC). Seizure activity was observed and scored for 2 hours post-administration; cerebral cortex tissues were collected to measure glutamate levels [1] |
| ADME/Pharmacokinetics |
In rats, after intravenous administration of cefoperazone sulfate (FK-037) (100 mg/kg, 200 mg/kg), the peak plasma concentrations (Cmax) at the end of infusion were 85 μg/mL (100 mg/kg) and 172 μg/mL (200 mg/kg), respectively [1]. The drug effectively crosses the blood-brain barrier, with cerebrospinal fluid/plasma concentration ratios of 0.25 (100 mg/kg) and 0.32 (200 mg/kg) one hour after administration [1]. The plasma protein binding rate in rats is approximately 15-20% [3]. Approximately 70-80% of the drug is excreted in the urine within 24 hours, of which approximately 90% is the unchanged drug [3]. The plasma elimination half-life in rats is approximately 1.2 hours [3].
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| Toxicity/Toxicokinetics |
In vitro experiments showed that cefoperazone sulfate (FK-037) at concentrations up to 200 μg/mL had no significant cytotoxicity to human HEp-2 cells [3]. In vivo experiments showed that cefoperazone sulfate could induce dose-dependent seizures in rats: 200 mg/kg intravenous injection caused generalized seizures in 80% of rats, while 100 mg/kg caused mild seizures in 30% of rats [1]. The acute intravenous LD50 in mice was >1500 mg/kg [3]. No significant toxicity was observed in rats treated with doses up to 100 mg/kg for 7 consecutive days (serum ALT/AST/creatinine levels did not change) [3]. Potential neurotoxicity (risk of seizures) is an important safety concern, especially in patients with high doses or impaired blood-brain barrier [1].
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| References |
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| Additional Infomation |
Cefoselis sulfate is a nitrogen-containing heterocyclic sulfate. It is functionally related to cephalosporin antibiotics.
See also: Cephalosporin antibiotics (note moved to). Cephalosporin sulfate (FK-037) is a fourth-generation broad-spectrum cephalosporin antibiotic[2][3] - Its antibacterial mechanism involves binding to bacterial penicillin-binding proteins (PBPs, especially PBP2 and PBP3), inhibiting bacterial cell wall synthesis, and ultimately leading to bacterial cell lysis[3] - It has good blood-brain barrier penetration, making it a potential candidate drug for treating central nervous system (CNS) infections caused by susceptible bacteria[1] - It is stable against most β-lactamases and effective against Gram-negative bacteria that produce extended-spectrum β-lactamases (ESBLs), but ineffective against strains that produce metallo-β-lactamases (MBLs)[2] - The main safety concern is dose-dependent neurotoxicity (induction of seizures), which is mediated by the release of glutamate from cortical neurons[1]- Due to poor oral bioavailability, there is no oral formulation available; it can only be administered intravenously.[3] |
| Molecular Formula |
C19H24N8O10S3
|
|---|---|
| Molecular Weight |
620.64
|
| Exact Mass |
620.077
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| Elemental Analysis |
C, 36.77; H, 3.90; N, 18.05; O, 25.78; S, 15.50
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| CAS # |
122841-12-7
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| Related CAS # |
Cefoselis;122841-10-5;Cefoselis hydrochloride;911212-25-4
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| PubChem CID |
9830519
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| Appearance |
White to off-white solid powder
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| LogP |
0.027
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| Hydrogen Bond Donor Count |
7
|
| Hydrogen Bond Acceptor Count |
17
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
40
|
| Complexity |
1100
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
S1C([H])([H])C(C([H])([H])N2C([H])=C([H])/C(=N\[H])/N2C([H])([H])C([H])([H])O[H])=C(C(=O)O[H])N2C([C@]([H])([C@@]12[H])N([H])C(/C(/C1=C([H])SC(N([H])[H])=N1)=N\OC([H])([H])[H])=O)=O.S(=O)(=O)(O[H])O[H]
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| InChi Key |
LZOLCSVRFKCSEM-ZQCAECPKSA-N
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| InChi Code |
InChI=1S/C19H22N8O6S2.H2O4S/c1-33-24-12(10-8-35-19(21)22-10)15(29)23-13-16(30)27-14(18(31)32)9(7-34-17(13)27)6-25-3-2-11(20)26(25)4-5-28;1-5(2,3)4/h2-3,8,13,17,20,28H,4-7H2,1H3,(H2,21,22)(H,23,29)(H,31,32);(H2,1,2,3,4)/b20-11?,24-12-;/t13-,17-;/m1./s1
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| Chemical Name |
(6R,7R)-7-((Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido)-3-((2-(2-hydroxyethyl)-3-imino-2,3-dihydro-1H-pyrazol-1-yl)methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid compound with sulfuric acid (1:1)
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| Synonyms |
Cefoselis sulfate; Cefoselis (sulfate); FK 037; 6EY42207VS; Cefoselis sulfate (JAN);
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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)
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| Solubility (In Vitro) |
Water : 5~14.29 mg/mL(~23.02 mM)
DMSO : 3~100 mg/mL ( 4.83~161.12 mM ) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.03 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.03 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (4.03 mM) Solubility in Formulation 5: 25 mg/mL (40.28 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6112 mL | 8.0562 mL | 16.1124 mL | |
| 5 mM | 0.3222 mL | 1.6112 mL | 3.2225 mL | |
| 10 mM | 0.1611 mL | 0.8056 mL | 1.6112 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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