| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
Purity: ≥98%
Sulopenem etzadroxil (PF-03709270; PF 03709270) is a novel, potent and orally bioavailable ester prodrug of sulopenem, with broad-spectrum antibacterial activity against most gram-positive and gram-negative bacteria. Sulopenem etzadroxil is a penem antibiotic agent that was more stable than imipenem against swine and human dehydropeptidase-Is. Sulopenem is one of the antibiotics that do not induce the appearance of subclones resistant to the drug.
On October 25, 2024, The U.S. Food and Drug Administration has approved Orlynvah (sulopenem etzadroxil and probenecid) oral tablets for the treatment of uncomplicated urinary tract infection(s) (uUTI) caused by certain bacteria (Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis) in adult women who have limited or no alternative oral antibacterial treatment options. Orlynvah is not indicated for the primary or step-down treatment of complicated UTI (cUTI) or complicated intra-abdominal infections (cIAI). Orlynvah is taken as one oral tablet twice daily for 5 days.| Targets |
β-lactamase
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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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Molecular Formula |
C19H27NO7S3
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|---|---|
| Molecular Weight |
477.615182161331
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| 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
|
| 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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