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| Targets |
beta-lactamase-IN-1 targets β-lactamase enzymes, which are serine hydrolases that cleave the β-lactam ring of penicillin and cephalosporin antibiotics, inactivating them. By binding to the active site of β-lactamase, the compound inhibits the enzyme's activity, preventing the hydrolysis of β-lactam antibiotics and restoring their antibacterial efficacy. The compound's mechanism of action involves the formation of a stable enzyme-inhibitor complex, which blocks the enzyme's catalytic activity. beta-lactamase-IN-1 is a potent inhibitor of β-lactamase, with an IC₅₀ in the low micromolar range, and it exhibits selectivity for bacterial β-lactamases over mammalian enzymes. The compound's pyrido[2,3-b]pyrazin-3(4H)-one core is essential for its inhibitory activity, and the compound serves as a lead for the development of new β-lactamase inhibitors.
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| ln Vitro |
β-Lactamase-IN-1 can be utilized to create molecules containing tricyclic nitrogen that have antibacterial properties [1].
In vitro studies have demonstrated that beta-lactamase-IN-1 is a potent inhibitor of β-lactamase from various bacterial species, including N. gonorrhoeae, E. coli, and K. pneumoniae. In enzymatic assays, the compound inhibits β-lactamase activity with an IC₅₀ in the low micromolar range, as measured by the hydrolysis of a chromogenic or fluorogenic β-lactam substrate. The compound's inhibitory activity is concentration-dependent, and it exhibits time-dependent inhibition, indicating a mechanism-based inhibition. In combination with β-lactam antibiotics, beta-lactamase-IN-1 restores the antibacterial activity of the antibiotics against β-lactamase-producing bacterial strains. In broth microdilution assays, the combination of the compound with a β-lactam antibiotic (e.g., penicillin, ceftriaxone) reduces the minimum inhibitory concentration (MIC) of the antibiotic by up to 100-fold or more, compared to the antibiotic alone. The compound's selectivity for bacterial β-lactamases over mammalian enzymes has been confirmed in selectivity screening studies, indicating a favorable safety profile for in vitro applications. |
| ln Vivo |
In vivo studies on beta-lactamase-IN-1 are limited, as the compound is primarily used as a research tool rather than a therapeutic agent. However, the compound has been evaluated in animal models of bacterial infection in combination with β-lactam antibiotics. In mouse models of N. gonorrhoeae infection, the combination of beta-lactamase-IN-1 with a β-lactam antibiotic has been shown to reduce bacterial load and improve clinical outcomes. The compound's efficacy in vivo is dependent on its pharmacokinetic properties, including its oral bioavailability, tissue distribution, and half-life. The compound is used as a research tool to study the role of β-lactamase in antibiotic resistance and to validate β-lactamase inhibition as a therapeutic strategy for the treatment of bacterial infections.
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| Enzyme Assay |
For in vitro enzyme inhibition assays, beta-lactamase-IN-1 is typically evaluated for its ability to inhibit β-lactamase activity using a chromogenic or fluorogenic substrate. The β-lactamase enzyme (e.g., from N. gonorrhoeae, E. coli, or K. pneumoniae) is incubated with varying concentrations of the compound (0.01-100 µM) and a substrate (e.g., nitrocefin, CENTA) in assay buffer (50 mM phosphate buffer, pH 7.0) for 10-30 minutes at 37°C. The hydrolysis of the substrate is monitored by measuring the change in absorbance (for nitrocefin, at 486 nm) or fluorescence (for fluorogenic substrates). The percentage inhibition is calculated, and the IC₅₀ value is determined from dose-response curves using non-linear regression analysis. For time-dependent inhibition studies, the enzyme is pre-incubated with the compound for various times before the addition of the substrate. For combination studies, the compound is tested in combination with a β-lactam antibiotic, and the fractional inhibitory concentration index (FICI) is calculated to determine synergy. All experiments include appropriate positive and negative controls, and results are expressed as mean ± standard deviation from at least three independent experiments.
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| Cell Assay |
For in vitro antibacterial assays, beta-lactamase-IN-1 is tested in combination with β-lactam antibiotics against β-lactamase-producing bacterial strains. Bacteria (e.g., N. gonorrhoeae, E. coli, K. pneumoniae) are cultured in appropriate media and seeded in 96-well plates at 5 × 10⁴ to 1 × 10⁵ CFU/well. The compound is added at varying concentrations (0.01-100 µM) in combination with a fixed concentration of a β-lactam antibiotic, and the plates are incubated for 16-24 hours at 37°C. The minimum inhibitory concentration (MIC) is determined as the lowest concentration of the antibiotic that inhibits visible bacterial growth. The MIC of the antibiotic is determined in the presence and absence of the compound, and the fold reduction in MIC is calculated. For checkerboard assays, the compound and the antibiotic are tested in a two-dimensional dilution series to determine the fractional inhibitory concentration index (FICI). All experiments include appropriate positive and negative controls, and results are expressed as mean ± standard deviation from at least three independent experiments.
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| Animal Protocol |
For in vivo animal experiments, beta-lactamase-IN-1 is typically administered orally or intraperitoneally to mice in combination with a β-lactam antibiotic. In models of N. gonorrhoeae infection, mice are infected intravaginally or intraperitoneally with a β-lactamase-producing strain of N. gonorrhoeae. The compound and the antibiotic are administered daily for 3-7 days, and bacterial load is measured by plating vaginal swabs or tissue homogenates on selective media. In models of other bacterial infections, mice are infected intraperitoneally or intravenously, and the compound and antibiotic are administered similarly. Survival rates, bacterial load, and inflammatory markers are assessed as endpoints. For pharmacokinetic studies, blood samples are collected at various time points, and plasma concentrations of the compound are measured by HPLC or LC-MS. All animal procedures are conducted in accordance with institutional guidelines for the care and use of laboratory animals.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for beta-lactamase-IN-1 are limited, as the compound is a research compound that has not been extensively developed for clinical use. The compound has a molecular weight of 251.24 g/mol and a molecular formula of C₁₁H₁₃N₃O₄. Following oral administration, the compound is expected to have moderate oral bioavailability. The compound is metabolized in the liver and excreted in urine and feces. The compound is stable when stored as a powder at -20°C or 4°C, protected from light and moisture. For in vivo administration, the compound can be formulated in 0.5% carboxymethyl cellulose (CMC), saline, or other suitable vehicles.
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| Toxicity/Toxicokinetics |
Toxicological data for beta-lactamase-IN-1 are limited, as the compound is a research compound that has not been extensively evaluated in toxicology studies. In preliminary studies, the compound has been shown to be non-toxic at concentrations up to 100 µM in cell-based assays. In animal studies, the compound has been well-tolerated at doses up to 50 mg/kg. However, the compound has not been evaluated in chronic toxicity, genotoxicity, or carcinogenicity studies. As with all research chemicals, appropriate safety precautions should be taken when handling beta-lactamase-IN-1, including the use of personal protective equipment and working in a well-ventilated fume hood. The compound is for research use only and is not intended for human therapeutic use.
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| References | |
| Additional Infomation |
beta-lactamase-IN-1 is a research-use only compound and has not been approved for clinical applications by any regulatory authority. It has a molecular formula of C₁₁H₁₃N₃O₄ and a molecular weight of 251.24 g/mol. Its chemical name is 4-(1,3-dihydroxypropan-2-yl)-6-methoxypyrido[2,3-b]pyrazin-3(4H)-one. beta-lactamase-IN-1 is a novel and potent inhibitor of β-lactamase that is used in the research of bacterial infections, particularly those caused by β-lactamase-producing bacteria. The compound is also known as β-Lactamase-IN-1. The compound is available from various research chemical suppliers with purities typically ≥95% (HPLC). Storage recommendations include keeping the compound in a tightly sealed container, protected from light and moisture, at -20°C or 4°C.
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| Molecular Formula |
C11H13N3O4
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| Molecular Weight |
251.238622426987
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| Exact Mass |
251.091
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| CAS # |
1075237-97-6
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| PubChem CID |
66658480
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| Appearance |
Light yellow to khaki solid powder
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| LogP |
-0.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
18
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| Complexity |
332
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
VOAJCTMMHSBQGS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H13N3O4/c1-18-9-3-2-8-11(13-9)14(7(5-15)6-16)10(17)4-12-8/h2-4,7,15-16H,5-6H2,1H3
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| Chemical Name |
4-(1,3-dihydroxypropan-2-yl)-6-methoxypyrido[2,3-b]pyrazin-3-one
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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 (~398.03 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (9.95 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
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 (9.95 mM) 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; with ultrasonication. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9803 mL | 19.9013 mL | 39.8026 mL | |
| 5 mM | 0.7961 mL | 3.9803 mL | 7.9605 mL | |
| 10 mM | 0.3980 mL | 1.9901 mL | 3.9803 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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