| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: =99.4%
| Targets |
Nacubactam targets multiple components of the bacterial cell wall synthesis and resistance machinery through a triple-action mechanism. Firstly, it acts as a potent inhibitor of serine β-lactamases, including Ambler classes A, C, and selected D enzymes. Secondly, it directly binds to penicillin-binding protein 2 (PBP2) in Enterobacteriaceae, conferring intrinsic antibacterial activity. Thirdly, it enhances the activity of partner β-lactam antibiotics, even against某些β-lactamase-negative strains. However, it lacks direct activity against class B metallo-β-lactamases (MBLs).
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| ln Vitro |
In vitro, nacubactam demonstrates potent inhibitory activity against a wide range of β-lactamases, restoring the activity of antibiotics like meropenem and cefepime against resistant strains. It possesses intrinsic antibacterial activity against Gram-negative bacilli due to its high affinity for PBP2. When combined with β-lactams such as aztreonam or cefepime, nacubactam produces substantial reductions in minimum inhibitory concentrations (MICs) against multidrug-resistant pathogens, including carbapenemase-producing Enterobacterales. In vivo, nacubactam has demonstrated efficacy in murine infection models. Pharmacokinetic/pharmacodynamic (PK/PD) studies in mice have been used to determine target values for the cefepime/nacubactam combination against β-lactamase-producing Enterobacterales. These preclinical models support its therapeutic potential against serious Gram-negative infections, including pneumonia.
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| ln Vivo |
In vivo, nacubactam has been evaluated in Phase 1, 2, and 3 clinical trials. Phase 1 studies in healthy volunteers showed it is generally well tolerated with favorable pharmacokinetics. A Phase 1 study demonstrated favorable intrapulmonary penetration of nacubactam, with an epithelial lining fluid (ELF) to plasma area under the curve ratio of 0.271, supporting its development for nosocomial pneumonia. The pivotal Phase 3 Integral-1 trial (N=614) evaluated cefepime-nacubactam and aztreonam-nacubactam versus imipenem-cilastatin for cUTI and acute pyelonephritis. Cefepime-nacubactam achieved an 82% clinical and microbiological success rate, significantly higher than the 61% for the control arm. Aztreonam-nacubactam showed a 72% success rate, meeting the non-inferiority criteria.
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| Enzyme Assay |
In vitro enzyme assays for nacubactam typically measure its ability to inhibit β-lactamase activity, often using a chromogenic or fluorogenic substrate. The compound is dissolved in a suitable solvent like DMSO and serially diluted in assay buffer. The enzyme (e.g., class A or C β-lactamase) is incubated with the substrate and varying concentrations of nacubactam. The rate of substrate hydrolysis is monitored spectrophotometrically or fluorometrically, and the IC₅₀ value is calculated from dose-response curves. Its binding affinity for PBP2 can be assessed using competition assays with a labeled penicillin, such as Bocillin FL, in membrane preparations from Enterobacteriaceae.
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| Cell Assay |
For cell-based assays, the in vitro antibacterial activity of nacubactam, alone or in combination, is evaluated using standard broth microdilution methods against a panel of bacterial isolates. Bacterial cultures are grown in appropriate media (e.g., Mueller-Hinton broth) and inoculated into 96-well plates containing serial two-fold dilutions of the test compound(s). The minimum inhibitory concentration (MIC) is determined as the lowest concentration that inhibits visible bacterial growth after overnight incubation at 35°C. The synergistic or additive effect of nacubactam with partner β-lactams can be assessed by checkerboard assays or by measuring the reduction in MIC of the β-lactam in the presence of a fixed concentration of nacubactam.
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| Animal Protocol |
In vivo, nacubactam is administered intravenously. In preclinical studies, it is typically given to rodent models of infection (e.g., thigh or pneumonia models) via intravenous or subcutaneous injection. In clinical trials, healthy volunteers or patients receive nacubactam as an intravenous infusion over 60 to 90 minutes. For the Phase 3 Integral-1 trial, patients with cUTI or acute pyelonephritis were randomized to receive intravenous cefepime-nacubactam, aztreonam-nacubactam, or imipenem-cilastatin. Efficacy was assessed by clinical and microbiological responses at a test-of-cure visit. Safety was monitored through adverse event reporting, clinical laboratory tests, and vital signs.
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| ADME/Pharmacokinetics |
Nacubactam (MW 324.31, C₉H₁₆N₄O₇S) is predominantly excreted unchanged in the urine, indicating minimal metabolic clearance. Its pharmacokinetics appear linear, with exposure increasing in an approximately dose-proportional manner across the dose range investigated (50 to 8,000 mg). It has a plasma half-life of approximately 1.71 hours. The compound shows favorable intrapulmonary penetration. Coadministration with β-lactams like meropenem, cefepime, or aztreonam does not significantly alter its pharmacokinetic profile. Metabolites (M1 and M2) are detected at low levels.
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| Toxicity/Toxicokinetics |
Nacubactam has been generally well tolerated in clinical trials. The most frequently reported adverse events were mild to moderate complications associated with intravenous access and headache. No serious adverse events, dose-limiting toxicities, or deaths related to the study drug were reported. There was no apparent relationship between drug dose and the pattern, incidence, or severity of adverse events. No clinically relevant dose-related trends were observed in laboratory safety test results. The compound is classified with GHS07 warning, indicating potential for acute toxicity.
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| References |
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| Additional Infomation |
Nacubactam is being investigated in the clinical trial NCT03174795 (a study of the pharmacokinetics of RO7079901 and meropenem in patients with complicated urinary tract infections).
Nacubactam is an investigational β-lactamase inhibitor developed by Meiji Seika Pharma. It has a unique triple mechanism of action: inhibiting serine β-lactamases (classes A, C, and some D), binding to PBP2, and enhancing partner β-lactam activity. It has received U.S. FDA Fast Track and Qualified Infectious Disease Product designations. Phase 1 studies in healthy Japanese and Chinese participants confirmed its favorable safety and PK profile. The Phase 3 Integral-1 trial, published in *The Lancet*, met its primary endpoints, with cefepime-nacubactam showing superior efficacy to imipenem-cilastatin for cUTI and pyelonephritis. The compound is not yet approved for clinical use. |
| Molecular Formula |
C9H16N4O7S
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|---|---|
| Molecular Weight |
324.311
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| Exact Mass |
324.074
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| Elemental Analysis |
C, 33.33; H, 4.97; N, 17.28; O, 34.53; S, 9.89
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| CAS # |
1452458-86-4
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| Related CAS # |
2007923-17-1 (hydrate);1452458-86-4 (free acid);
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| PubChem CID |
73386748
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| Appearance |
Off-white to beige solid powder
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| LogP |
-4.6
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
21
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| Complexity |
519
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1C[C@H](N2C[C@@H]1N(C2=O)OS(=O)(=O)O)C(=O)NOCCN
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| InChi Key |
RSBPYSTVZQAADE-RQJHMYQMSA-N
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| InChi Code |
InChI=1S/C9H16N4O7S/c10-3-4-19-11-8(14)7-2-1-6-5-12(7)9(15)13(6)20-21(16,17)18/h6-7H,1-5,10H2,(H,11,14)(H,16,17,18)/t6-,7+/m1/s1
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| Chemical Name |
(1R,2S,5R)-2-((2-aminoethoxy)carbamoyl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl hydrogen sulfate
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| Synonyms |
RG-6080; RG 6080; RG6080; FPI-1459; FPI 1459; FPI1459; OP-0595; OP 0595; OP0595; Nacubactam;
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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) |
DMSO : ~250 mg/mL (~770.87 mM)
H2O : ~50 mg/mL (~154.17 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.41 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 20.8 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: ≥ 2.08 mg/mL (6.41 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 20.8 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: ≥ 2.08 mg/mL (6.41 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: 100 mg/mL (308.35 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 | 3.0835 mL | 15.4173 mL | 30.8347 mL | |
| 5 mM | 0.6167 mL | 3.0835 mL | 6.1669 mL | |
| 10 mM | 0.3083 mL | 1.5417 mL | 3.0835 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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