| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
β-lactamase
Sulopenem etzadroxil targets bacterial penicillin-binding proteins (PBPs) through its active metabolite sulopenem. As a thiopenem antibiotic, sulopenem is a β-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to PBPs, which are enzymes involved in the final stages of peptidoglycan synthesis. By inhibiting PBPs, sulopenem disrupts the integrity of the bacterial cell wall, leading to cell lysis and death. Sulopenem etzadroxil is a prodrug that is converted to the active sulopenem upon oral administration. Sulopenem has broad-spectrum antibacterial activity against most gram-positive and gram-negative bacteria. The compound has shown promising activity against multidrug-resistant (MDR) pathogens. |
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| ln Vitro |
Sulopenem has _in vitro_ activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of sulopenem results from the inhibition of cell wall synthesis and is mediated through sulopenem binding to penicillin binding proteins (PBPs). Sulopenem's β-lactam ring alkylates the serine residues of PBPs, ultimately inhibiting peptidoglycan cross-linking.
Sulopenem, similar to other beta-lactam antibacterials, exhibits time-dependent bacterial inhibition. The percentage of time that unbound plasma concentrations of sulopenem exceed the sulopenem minimum inhibitory concentration (MIC) against the infecting organism has been shown to best correlate with efficacy in _in vitro_ models of infection. In E. coli_, sulopenem demonstrated binding affinity for PBPs in the following order: PBP2 > PBP1A > PBP1B > PBP4 > PBP3 > PBP5/6. Sulopenem etzadroxil is a prodrug of the penem antibacterial [sulopenem]. Like other beta-lactam antibacterials, it is a time-dependent inhibitor of bacterial cell wall synthesis. Sulopenem etzadroxil was approved by the FDA in October 2024 for the treatment of uncomplicated urinary tract infections. It is administered in combination with [probenecid] in order to increase antibiotic exposure. Sulopenem etzadroxil demonstrates in vitro antibacterial activity through its active metabolite sulopenem. Sulopenem is a thiopenem antibiotic with broad-spectrum antibacterial activity against most gram-positive and gram-negative bacteria. The compound has shown promising biological activity against various strains of bacteria, particularly those resistant to conventional antibiotics. Detailed in vitro activity data, including MIC values against clinical isolates, are available in the primary literature. Sulopenem etzadroxil's prodrug design allows for oral administration of the antibiotic, which is important for outpatient treatment of infections. |
| ln Vivo |
Sulopenem etzadroxil is indicated in combination with [probenecid] for the treatment of uncomplicated urinary tract infections caused by _Escherichia coli_, _Klebsiella pneumoniae_, or _Proteus mirabilis_ in adult women who have limited or no alternative oral antibacterial treatment options.
Sulopenem Etzadroxil is an orally available ester prodrug form of sulopenem, a thiopenem with broad-spectrum antibacterial activity against most gram-positive and gram-negative bacteria. After oral administration of sulopenem etzadroxil, the ester bond is cleaved, releasing active sulopenem. Sulopenem is not active against Pseudomonas aeruginosa. In addition, this agent is fairly stable against hydrolysis by various beta-lactamases. Sulopenem etzadroxil has been evaluated in vivo for its antibacterial activity. The compound is an orally active prodrug of the antibiotic sulopenem. Sulopenem etzadroxil is active in mice infected with Bacillus anthracis. The compound has been investigated in clinical trials for the treatment of urinary tract infections (Phase III) and bacterial pneumonia. The compound's oral bioavailability and broad-spectrum antibacterial activity support its utility for studying bacterial infections and for evaluating oral carbapenem-like antibiotics. Detailed in vivo efficacy data are available in the primary literature and clinical trial reports. |
| Enzyme Assay |
The in vitro antibacterial susceptibility assay for Sulopenem etzadroxil measures the minimum inhibitory concentration (MIC) of the compound's active metabolite sulopenem against bacterial pathogens. Broth microdilution or agar dilution methods are used according to CLSI or EUCAST guidelines. Serial two-fold dilutions of sulopenem (the active metabolite) are prepared in appropriate medium. Bacterial inocula are standardized and added to each well or plate. After incubation at 35-37°C for 16-20 hours, the MIC is determined as the lowest concentration that inhibits visible bacterial growth. The compound is dissolved in DMSO or appropriate solvent and diluted in medium. Quality control strains are included in each assay run to ensure validity.
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| Cell Assay |
The in vitro cellular assay for Sulopenem etzadroxil is not applicable as the compound targets bacterial cell wall synthesis and is not intended for use in mammalian cell-based assays. However, cytotoxicity assays may be performed using mammalian cell lines to assess the compound's safety profile. Cells are cultured in appropriate medium and treated with varying concentrations of sulopenem etzadroxil or vehicle control (DMSO) for specified time points. Cell viability is assessed using assays such as MTT or CellTiter-Glo. Cytotoxicity is quantified, and IC50 values are determined. These assays help to assess the selectivity of the compound for bacterial versus mammalian cells.
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| Animal Protocol |
In vivo animal experiments with Sulopenem etzadroxil are conducted using mouse models of bacterial infection. Animals are infected with bacterial pathogens such as Bacillus anthracis or other susceptible strains. Sulopenem etzadroxil is administered orally at various doses. Bacterial load in tissues (e.g., blood, lungs, spleen) is measured by bacterial colony counting at various time points post-infection. Survival rates and clinical signs of infection are monitored. The compound's antibacterial efficacy is evaluated by comparing bacterial load and survival in treated versus control groups. Detailed experimental protocols are described in the primary literature.
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| ADME/Pharmacokinetics |
Absorption
After rapid conversion to the active ingredient, sulopenem has a bioavailability of approximately 40% on an empty stomach, which increases to 64% when taken with food. Excretion In healthy adult subjects, following a single oral administration of radiolabeled Sulopenem etzadroxil, 44.3% of the radioactive product was excreted in feces (26.9% of which was unmetabolized sulopenem), and 40.8% was excreted in urine (3.1% of which was unmetabolized sulopenem). Volume of Distribution On an empty stomach, the apparent volume of distribution of sulopenem is 134 L. When taken with a high-fat meal, the apparent volume of distribution is 92.09 L. Clearance On an empty stomach, the apparent clearance of sulopenem is 77.6 L/h. When taken with a high-fat meal, the apparent clearance is 50.55 L/h. Protein Binding Sulopene has very low protein binding in plasma (approximately 11%). Metabolites/Metabolites After oral administration, Sulopenem etzadroxil is hydrolyzed by esterases to the active drug sulopenem, which is further metabolized by hydrolysis and dehydrogenation. Two inactive metabolites of sulopenem—M1a and M1b—have been identified, accounting for 21.8% and 43.6% of circulating radioactivity, respectively, after administration of a radiolabeled dose. Biological Half-Life The mean elimination half-life of sulopenem is 1.18 hours in the fasting state. When taken with a high-fat meal, the mean elimination half-life is 1.28 hours. Detailed pharmacokinetic (PK) parameters for Sulopenem etzadroxil are available from clinical studies. The compound is an orally available prodrug that is converted to the active sulopenem. Sulopenem etzadroxil has a molecular weight of 477.6 and a chemical formula of C19H27NO7S3. The compound should be stored long-term in a cool, dry place. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are available in the primary literature and clinical trial reports and should be consulted for specific experimental planning. |
| Toxicity/Toxicokinetics |
Safety Information
Prescribing information includes warnings about hypersensitivity reactions, Clostridium difficile-associated diarrhea (CDAD), and the possibility of exacerbating gout when used in patients with a known history of gout. Orlynvah is contraindicated in patients with a history of hypersensitivity to any component of Orlynvah (sulfapyridine ethamsylate and probenecid) or other β-lactam antibiotics, patients with a known blood disorder, patients with a known uric acid kidney stone, and patients currently taking ketorolac tromethamine. The most common side effects of Orlynvah include diarrhea, nausea, vaginal yeast infection, headache, and vomiting. Comprehensive toxicological data for Sulopenem etzadroxil are available from preclinical and clinical studies. As a research-grade compound, Sulopenem etzadroxil is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. Toxicological data from clinical studies are available in the published literature and should be consulted for safety information. |
| References |
[1]. Antimicrob Agents Chemother. 2009 Jun;53(6):2239-47.
[2]. https://pubchem.ncbi.nlm.nih.gov/compound/23642298 |
| Additional Infomation |
Sulopenem etzadroxil is currently undergoing clinical trial NCT03354598 (a comparison of the efficacy of oral Sulopenem etzadroxil/probenecid versus ciprofloxacin in the treatment of uncomplicated urinary tract infections in adult women). Sulopenem etzadroxil is an oral ester prodrug of sulopenem, a thiopenem antibiotic with broad-spectrum antibacterial activity against most Gram-positive and Gram-negative bacteria. After oral administration of Sulopenem etzadroxil, the ester bond breaks, releasing active sulopenem. Sulopenem is ineffective against Pseudomonas aeruginosa. Furthermore, this drug exhibits good stability against hydrolysis by various β-lactamases.
Efficacy The efficacy of Orlynvah was evaluated in two phase 3 randomized, double-blind, controlled clinical trials (Trial 1 and Trial 2), both of which enrolled adult women with urinary tract infections. Orlynvah was administered twice daily, one tablet each time, for 5 days. Trial 1 (NCT05584657) was a non-inferiority trial that enrolled 2214 adult women with urinary tract infections (UTIs) and randomized them to receive treatment. Orlynvah demonstrated efficacy in patients with amoxicillin/clavulanate-sensitive pathogens, with a composite response rate (combined microbiological and clinical remission) of 62%, compared to 55% in the amoxicillin/clavulanate group. Trial 2 (NCT03354598) was a non-inferiority trial that enrolled 1660 adult women with UTIs and randomized them to receive treatment. Orlynvah demonstrated efficacy in patients with ciprofloxacin-resistant pathogens, with a composite response rate of 48%, compared to 33% in the ciprofloxacin group. A total of 1932 patients received Orlynvah treatment in both trials. Clinical trials evaluating Orlynvah for complicated UTIs (cUTIs) and complicated intra-abdominal infections (cIAIs) have not demonstrated efficacy. Sulopenem etzadroxil is a research compound and clinical-stage antibiotic developed for studying and treating bacterial infections, particularly those caused by multidrug-resistant pathogens. The compound is an orally available ester prodrug of sulopenem, a thiopenem antibiotic with broad-spectrum antibacterial activity. Sulopenem etzadroxil is also known as PF-03709270. The compound has been investigated in clinical trials for urinary tract infections (Phase III) and bacterial pneumonia. Sulopenem etzadroxil is available from various chemical suppliers for research purposes. Its utility lies in its oral bioavailability and activity against resistant bacterial pathogens. |
| Molecular Formula |
C19H27NO7S3
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|---|---|
| Molecular Weight |
477.615182161331
|
| Exact Mass |
477.094
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| Elemental Analysis |
C, 47.78; H, 5.70; N, 2.93; O, 23.45; S, 20.14
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| CAS # |
1000296-70-7
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| PubChem CID |
23642298
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| Appearance |
White to light yellow solid powder
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| LogP |
2.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
30
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| Complexity |
767
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| Defined Atom Stereocenter Count |
5
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| SMILES |
CCC(CC)C(=O)OCOC(=O)C1=C(S[C@H]2N1C(=O)[C@@H]2[C@@H](C)O)S[C@H]3CC[S@@](=O)C3
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| InChi Key |
NBPVNGWRLGHULH-JKOUTOBWSA-N
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| InChi Code |
InChI=1S/C19H27NO7S3/c1-4-11(5-2)17(23)26-9-27-18(24)14-19(28-12-6-7-30(25)8-12)29-16-13(10(3)21)15(22)20(14)16/h10-13,16,21H,4-9H2,1-3H3/t10-,12+,13+,16-,30?/m1/s1
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| Chemical Name |
((2-ethylbutanoyl)oxy)methyl (5R,6S)-6-((R)-1-hydroxyethyl)-3-(((3S)-1-oxidotetrahydrothiophen-3-yl)thio)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
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| Synonyms |
PF-03709270; PF03709270; SULOPENEM ETZADROXIL; 1000296-70-7; Sulopenem etzadroxil (USAN); Sulopenem etzadroxil [USAN]; 492M3I304T; PF 03709270; PF-3709270; PF3709270; PF 3709270.
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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 |
| 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) |
DMSO : ~100 mg/mL (~209.37 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.23 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 (5.23 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 (5.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0937 mL | 10.4686 mL | 20.9371 mL | |
| 5 mM | 0.4187 mL | 2.0937 mL | 4.1874 mL | |
| 10 mM | 0.2094 mL | 1.0469 mL | 2.0937 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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