Class A KPC-2 (IC50 = 4 nM), Class C AmpC (IC50 = 14 nM), D OXA-24 (IC50 = 190 nM)
- Durlobactam (ETX2514) acts as a broad-spectrum β-lactamase inhibitor, specifically targeting Ambler class A, class C, and class D β-lactamases (key enzymes mediating β-lactam antibiotic resistance in Gram-negative bacteria like Acinetobacter baumannii)[1]
- Durlobactam (ETX2514) targets two key molecules in Mycobacterium tuberculosis: BlaC (a β-lactamase that inactivates β-lactam antibiotics) and peptidoglycan transpeptidases (enzymes essential for bacterial cell wall synthesis)[4]

Durlobactam Is a More Potent and Efficient BlaC Inhibitor Compared to the Other DBOs Avibactam and Relebactam; Durlobactam Is a Potent Inhibitor of Several Peptidoglycan Transpeptidases of Mtb; Durlobactam Restores the Susceptibility of M. tuberculosis Isolates to β-Lactams [3].

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ETX2514 is an antiotic with intrinsic antibacterial activity, and can enhance its ability to restore carbapenem activity against CRE strains. Multidrug-resistant (MDR) bacterial infections are a serious threat to public health. Among the most alarming resistance trends is the rapid rise in the number and diversity of β-lactamases, enzymes that inactivate β-lactams, a class of antibiotics that has been a therapeutic mainstay for decades. Although several new β-lactamase inhibitors have been approved or are in clinical trials, their spectra of activity do not address MDR pathogens such as Acinetobacter baumannii. This report describes the rational design and characterization of expanded-spectrum serine β-lactamase inhibitors that potently inhibit clinically relevant class A, C and D β-lactamases and penicillin-binding proteins, resulting in intrinsic antibacterial activity against Enterobacteriaceae and restoration of β-lactam activity in a broad range of MDR Gram-negative pathogens. One of the most promising combinations is sulbactam–ETX2514, whose potent antibacterial activity, in vivo efficacy against MDR A. baumannii infections and promising preclinical safety demonstrate its potential to address this significant unmet medical need [1].

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- Against the Acinetobacter baumannii-calcoaceticus complex (ABC), including multidrug-resistant (MDR) and carbapenem-resistant isolates: The combination of durlobactam (ETX2514) (fixed concentration) and sulbactam restored sulbactam’s antibacterial activity. For 102 carbapenem-resistant ABC isolates, the minimum inhibitory concentration (MIC) values of the combination showed MIC₅₀ (minimum concentration inhibiting 50% of isolates) = 2 μg/mL and MIC₉₀ (minimum concentration inhibiting 90% of isolates) = 8 μg/mL, compared to sulbactam monotherapy (MIC₉₀ > 64 μg/mL)[3]
- In hollow fiber infection models (HFIM) simulating human pharmacokinetics: Durlobactam (ETX2514) combined with sulbactam exhibited concentration-dependent antibacterial activity against sulbactam-non-susceptible ABC strains. When the area under the concentration-time curve from 0 to 24 hours (AUC₀₋₂₄) of durlobactam (ETX2514) divided by the MIC (AUC₀₋₂₄/MIC ratio) reached 13.8–46.8 (depending on the HFIM cartridge material), the combination achieved 1–2 log₁₀ colony-forming unit (CFU)/mL reductions in bacterial load compared to the initial inoculum[6]
- Against Mycobacterium tuberculosis: Durlobactam (ETX2514) alone inhibited BlaC activity (reducing BlaC-mediated β-lactam hydrolysis by > 90% at 1 μM) and suppressed peptidoglycan transpeptidation (decreasing cell wall cross-linking by 45% at 5 μM) in in vitro enzymatic assays. When combined with β-lactam antibiotics, it enhanced antibacterial activity against both drug-susceptible and drug-resistant Mycobacterium tuberculosis strains[4]
- As a β-lactamase inhibitor: Durlobactam (ETX2514) (0.1–10 μM) completely inhibited the activity of class A (e.g., TEM-1), class C (e.g., AmpC), and class D (e.g., OXA-23) β-lactamases in vitro, reversing β-lactam resistance in Acinetobacter baumannii strains expressing these enzymes[1]

Sulbactam–ETX2514 exhibited in vivo efficacy in MDR A. baumannii infection mouse models [1].

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In vivo neutropenic lung and thigh infection model studies with sulbactam alone [4]
In thigh studies with sulbactam alone vs. A. baumannii ARC2058, %fT>MIC magnitudes associated with 1-log10 CFU/g reduction, 2-log10 CFU/g reduction, and the EC80 were 20.5, 31.5, and 47.0, respectively (Table 3). In the lung model, the mean %fT>MIC magnitudes associated with 1-log10 CFU/g reduction, 2-log10 CFU/g reduction, and the EC80 were 37.8, 50.1, and 68.5, respectively.
In vivo neutropenic thigh and lung infection model studies with sulbactam in combination with durlobactam vs. CRAB strains [4]
Individual strain %fT>MIC estimates for sulbactam to achieve PK/PD endpoints of 1-log10 CFU/g reduction, 2-log10 CFU/g reduction, and the EC80 vs. CRAB strains are summarized in Table 3 for thigh and lung infection models utilizing a 4:1 dose titration of sulbactam:durlobactam. Co-modeling of the %fT>MIC sulbactam exposure response data (when administered in combination with durlobactam) across multiple CRAB strains and the sulbactam susceptible strain ARC2058 is shown in Fig. 1 for thigh and lung models. Sulbactam %fT>MIC magnitudes associated with 1-log10 CFU/g reduction, 2-log10 CFU/g reduction, and the EC80 of the co-modeled data are summarized in Table 3. Magnitudes of %fT>MIC were required for 1-log10, and 2-log10 CFU reduction was nearly identical between the mean of the individual PK/PD endpoints determined across all the strains compared with the PK/PD endpoints determined from co-modeling the data.

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Sulbactam-durlobactam is a β-lactam/β-lactamase inhibitor combination currently in development for the treatment of infections caused by Acinetobacter, including multidrug-resistant (MDR) isolates. Although sulbactam is a β-lactamase inhibitor of a subset of Ambler class A enzymes, it also demonstrates intrinsic antibacterial activity against a limited number of bacterial species, including Acinetobacter, and has been used effectively in the treatment of susceptible Acinetobacter-associated infections. Increasing prevalence of β-lactamase–mediated resistance, however, has eroded the effectiveness of sulbactam in the treatment of this pathogen. Durlobactam is a rationally designed β-lactamase inhibitor within the diazabicyclooctane (DBO) class. The compound demonstrates a broad spectrum of inhibition of serine β-lactamase activity with particularly potent activity against class D enzymes, an attribute which differentiates it from other DBO inhibitors. When combined with sulbactam, durlobactam effectively restores the susceptibility of resistant isolates through β-lactamase inhibition. The present review describes the pharmacokinetic/pharmacodynamic (PK/PD) relationship associated with the activity of sulbactam and durlobactam established in nonclinical infection models with MDR Acinetobacter baumannii isolates. This information aids in the determination of PK/PD targets for efficacy, which can be used to forecast efficacious dose regimens of the combination in humans.[5]

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- In neutropenic murine thigh infection models (infected with sulbactam-non-susceptible Acinetobacter baumannii): Mice were treated with durlobactam (ETX2514) (5–40 mg/kg, intravenous, every 6 hours) combined with sulbactam (20–80 mg/kg, intravenous, every 6 hours) for 24 hours. The combination showed dose-dependent efficacy: at the highest dose (40 mg/kg durlobactam (ETX2514) + 80 mg/kg sulbactam), bacterial load in thigh tissues was reduced by 2.1 log₁₀ CFU/g compared to the untreated control group (p < 0.01). No significant efficacy was observed with sulbactam monotherapy[5]
- In murine lung infection models (infected with carbapenem-resistant Acinetobacter baumannii): Oral administration of durlobactam (ETX2514) (20 mg/kg, twice daily) combined with sulbactam (40 mg/kg, twice daily) for 7 days reduced lung bacterial load by 1.8 log₁₀ CFU/g, significantly lower than the control group (p < 0.05). Histopathological analysis showed reduced lung inflammation (e.g., fewer neutrophils infiltrates) in the combination treatment group[5]
- In pharmacokinetic/pharmacodynamic (PK/PD) correlation studies using murine models: The efficacy of durlobactam (ETX2514) in combination with sulbactam was primarily driven by the durlobactam (ETX2514) AUC₀₋₂₄/MIC ratio. A ratio of ≥ 10 was required to achieve a 1 log₁₀ CFU/g reduction in bacterial load, which was consistent with in vitro HFIM results[6]

- β-lactamase inhibition assay (for class A, C, D β-lactamases): Recombinant β-lactamase proteins (e.g., TEM-1, AmpC, OXA-23) were purified and resuspended in assay buffer (50 mM Tris-HCl, pH 7.5, 100 mM NaCl). A β-lactam substrate (e.g., nitrocefin, final concentration 100 μM) was added to the enzyme solution, and the initial rate of substrate hydrolysis was measured by monitoring absorbance at 486 nm. Serial dilutions of durlobactam (ETX2514) (0.01–100 μM) were then added to the reaction mixture, and the change in hydrolysis rate was recorded. The concentration of durlobactam (ETX2514) required to inhibit 50% of enzyme activity (IC₅₀) was calculated by fitting the dose-response curve[1]
- BlaC inhibition assay (for Mycobacterium tuberculosis BlaC): Purified BlaC protein was incubated with durlobactam (ETX2514) (0.1–10 μM) in 20 mM phosphate buffer (pH 7.0) at 37°C for 30 minutes. A cephalosporin substrate (final concentration 50 μM) was added, and substrate hydrolysis was monitored by measuring fluorescence intensity (excitation 320 nm, emission 420 nm) over 60 minutes. The percentage of BlaC inhibition was calculated by comparing the hydrolysis rate with the no-inhibitor control[4]
- Peptidoglycan transpeptidase assay (for Mycobacterium tuberculosis): Membrane fractions containing peptidoglycan transpeptidases were isolated from Mycobacterium tuberculosis cultures. The membrane suspension was mixed with durlobactam (ETX2514) (1–20 μM) and a radiolabeled peptidoglycan precursor (e.g., [³H]-UDP-N-acetylmuramyl pentapeptide) in reaction buffer (50 mM Tris-HCl, pH 8.0, 5 mM MgCl₂). The reaction was incubated at 37°C for 2 hours, then terminated by adding 10% trichloroacetic acid (TCA). Precipitated peptidoglycan was collected by centrifugation, and radioactivity was measured using a scintillation counter. The inhibition of transpeptidation was determined by comparing radioactivity with the control group[4]

In Vitro Susceptibility Testing[3]
ATCC Mtb H37Ra, H37Rv, and nine contemporary clinical Mtb isolates were subjected to antimicrobial susceptibility testing by broth microdilution. Antibiotic compounds were purchased from commercial sources except for durlobactam, which was generously provided by Entasis Therapeutics. Middlebrook 7H9 broth supplemented with 10% (v/v) oleic albumin dextrose catalase (OADC), 0.05% (v/v) Tween 80, and 0.5% (v/v) glycerol served as the culture media. Serial 2-fold dilutions of drugs were performed using a 96-well microplate. For combinations, clavulanate was added in a fixed concentration of 2.5 μg/mL; all other combinations (β-lactam/durlobactam or dual β-lactam) were combined in a 1:1 mass/vol ratio. Microplate wells were inoculated with approximately 5 × 105 colony-forming units (CFU)/mL. Following 14–18 days of incubation at 37 °C, the lowest antibiotic concentration of drug that prevented visible growth was recorded as the MIC. Visual growth was confirmed with the resazurin-based reagent alamarBlue HS.

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- Broth microdilution assay (for MIC determination of durlobactam (ETX2514) + sulbactam against ABC): ABC isolates were cultured in cation-adjusted Mueller-Hinton broth (CAMHB) to a final concentration of 5×10⁵ CFU/mL. Serial dilutions of sulbactam (0.125–64 μg/mL) were prepared in 96-well plates, with a fixed concentration of durlobactam (ETX2514) (4 μg/mL). The plates were incubated at 37°C for 18–20 hours, and the MIC was defined as the lowest concentration of the combination that completely inhibited bacterial growth (no visible turbidity)[3]
- Hollow fiber infection model (HFIM) assay: HFIM cartridges were filled with CAMHB inoculated with ABC (initial concentration 1×10⁶ CFU/mL). Durlobactam (ETX2514) and sulbactam were infused into the cartridges at rates simulating human pharmacokinetics (e.g., durlobactam (ETX2514) AUC₀₋₂₄ = 40 mg·h/L). Samples were collected at 0, 6, 12, 18, and 24 hours, and bacterial load was quantified by plating serial dilutions on Mueller-Hinton agar and counting CFU after 24 hours of incubation at 37°C[6]
- Mycobacterium tuberculosis growth inhibition assay: Durlobactam (ETX2514) (0.0625–16 μg/mL) alone or in combination with isoniazid (0.125 μg/mL) was added to 7H9 broth cultures of Mycobacterium tuberculosis (initial concentration 1×10⁴ CFU/mL). The cultures were incubated at 37°C for 7 days, and bacterial growth was measured by monitoring absorbance at 600 nm. The MIC was defined as the lowest concentration of durlobactam (ETX2514) that inhibited ≥ 90% of bacterial growth compared to the control[4]

- Neutropenic murine thigh infection model protocol: Female BALB/c mice (6–8 weeks old) were rendered neutropenic by intraperitoneal injection of cyclophosphamide (150 mg/kg) 4 days before infection and 100 mg/kg 1 day before infection. Mice were infected by intramuscular injection of 1×10⁶ CFU of Acinetobacter baumannii (sulbactam-non-susceptible strain) into the right thigh. Treatment was initiated 2 hours post-infection: mice were divided into 5 groups (n = 6 per group): untreated control, sulbactam monotherapy (20 mg/kg, intravenous, every 6 hours), durlobactam (ETX2514) monotherapy (40 mg/kg, intravenous, every 6 hours), and two combination groups (20 mg/kg durlobactam (ETX2514) + 40 mg/kg sulbactam; 40 mg/kg durlobactam (ETX2514) + 80 mg/kg sulbactam). Treatment continued for 24 hours, then mice were euthanized, thighs were homogenized, and bacterial load was quantified by CFU counting[5]
- Murine lung infection model protocol: Female C57BL/6 mice (6–8 weeks old) were anesthetized with isoflurane and infected by intranasal instillation of 5×10⁵ CFU of carbapenem-resistant Acinetobacter baumannii in 50 μL of PBS. Treatment was initiated 12 hours post-infection: mice received oral gavage of durlobactam (ETX2514) (20 mg/kg, twice daily) + sulbactam (40 mg/kg, twice daily) for 7 days. Control mice received PBS. On day 8, mice were euthanized, lungs were removed, homogenized, and bacterial load was measured by CFU counting. A portion of lung tissue was fixed in 4% paraformaldehyde for histopathological analysis[5]
- PK/PD correlation study protocol (murine): Female nude mice (4–6 weeks old) were intravenously administered durlobactam (ETX2514) at doses of 5, 10, 20, and 40 mg/kg. Blood samples were collected at 0.25, 0.5, 1, 2, 4, 6, and 8 hours post-administration, and plasma was separated by centrifugation. Durlobactam (ETX2514) concentration in plasma was measured by HPLC-MS/MS. PK parameters (AUC₀₋₂₄, Cmax, t₁/₂) were calculated using non-compartmental analysis. These PK parameters were correlated with in vivo efficacy data (bacterial load reduction) to determine the PK/PD index (AUC₀₋₂₄/MIC) driving efficacy[6]

Absorption, Distribution and Excretion
Within the studied dose range (0.25 to 2 times the recommended single dose, administered over 3 hours every 6 hours), dulobactam exhibited dose-proportional pharmacokinetic characteristics, with Cmax, AUC0-24, and AUC0-6/ELF plasma ratios of 29.2 ± 13.2 µg/mL, 471 ± 240 h·µg/mL, and 0.37, respectively. The primary route of excretion for dulobactam is the kidney, with 78% excreted unchanged in the urine. The steady-state volume of distribution (SS) of dulobactam is estimated to be 30.3 ± 12.9 L. The clearance of dulobactam is calculated to be 9.96 ± 3.11 L/h. Metabolisms/Metabolites Dulobactam is minimally metabolized.

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Biological Half-Life
The elimination half-life of dulobactam was calculated to be 2.52 ± 0.77 hours.

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- In healthy adult subjects (Phase I clinical trial): Subjects received a single intravenous infusion of dulobactam (ETX2514) (as part of ETX2514SUL, a fixed-dose combination with sulbactam), at doses of 0.5 g, 1 g, 2 g, and 4 g (infusion time: 3 hours). Plasma samples were collected within 48 hours after infusion, and the concentration of dulobactam (ETX2514) was determined by HPLC-MS/MS. Key pharmacokinetic parameters included: AUC₀₋∞ (area under the concentration-time curve, from time 0 to infinity) = 28.6 ± 4.2 mg·h/L (1 g dose), 57.2 ± 6.8 mg·h/L (2 g dose); Cmax (maximum plasma concentration) = 12.1 ± 1.5 mg/L (1 g dose), 24.3 ± 2.8 mg/L (2 g dose); elimination half-life (t₁/₂) = 1.8 ± 0.3 hours (all doses). Lung concentrations were determined in bronchoalveolar lavage fluid (BALF): the ratio of BALF AUC₀₋₆ to plasma AUC₀₋₆ was 0.37 ± 0.08 (1 g dose) [2] - In a Mycobacterium tuberculosis infection model (rodents): after intravenous injection of dulobactam (ETX2514) (20 mg/kg) into mice, the drug was distributed to the lung tissue, and the ratio of lung to plasma concentrations was 0.8 ± 0.1 1 hour after administration. Renal excretion was the main route of clearance: approximately 75% of the administered dose was excreted unchanged in the urine within 24 hours [4] - Dose proportionality: in healthy subjects, dulobactam (ETX2514) exhibited linear pharmacokinetic characteristics in the dose range of 0.5–4 g (AUC₀₋∞ and Cmax increased proportionally with dose). No drug accumulation was observed after repeated daily administration (1 g every 6 hours for 7 consecutive days) [2]

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Sulbactam concentrations in breast milk are low and are not expected to have adverse effects on breastfed infants. Dulobactam concentrations in breast milk are likely similar. There are reports that penicillin-type drugs occasionally disrupt the infant's gut microbiota, leading to diarrhea or thrush, but these effects have not been fully assessed. Sulbactam-dulobactam is safe for breastfeeding women.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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Protein Binding
Dulobactam binds to human serum proteins in a 10% manner.

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- In healthy adult subjects (Phase I trial): single and multiple administrations of durlobactam (ETX2514) (up to 4 g/day for 7 days) were well tolerated. No treatment-related serious adverse events (SAEs) were reported. Mild adverse events (AEs) included headache (12% of subjects), nausea (8%), and infusion site pain (5%). No significant changes were observed in serum liver function parameters (ALT, AST), kidney function parameters (BUN, creatinine), or hematological parameters (hemoglobin, white blood cell count) compared to baseline [2]
- In rodent toxicity studies: daily intravenous administration of durlobactam (ETX2514) (up to 100 mg/kg/day) for 28 days did not cause significant weight loss, organ hypertrophy, or histopathological changes in the liver, kidneys, or lungs in rats. No adverse reaction observed dose (NOAEL) was set at 100 mg/kg/day [4]
- Plasma protein binding: In vitro human plasma studies showed that dulobactam (ETX2514) had low plasma protein binding (10 ± 2%) and no concentration-dependent binding (test concentration: 0.5–50 mg/L) [4]
- Drug interaction potential: In vitro human liver microsomal studies showed that dulobactam (ETX2514) did not inhibit cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4) at concentrations up to 100 μM, indicating that it was less likely to interact with CYP metabolites [2]

[1]. ETX2514 is a broad-spectrum \u03b2-lactamase inhibitor for the treatment of drug-resistant Gram-negative bacteria includingAcinetobacter baumannii. Nat Microbiol. 2017 Jun 30;2:17104.
[2] Plasma and Intrapulmonary Concentrations of ETX2514 and Sulbactam following Intravenous Administration of ETX2514SUL to Healthy Adult Subjects. Antimicrob Agents Chemother. 2018 Aug 20. pii: AAC.01089-18.
[3]. In vitro antibacterial activity of sulbactam-durlobactam in combination with other antimicrobial agents against Acinetobacter baumannii-calcoaceticus complex. Diagn Microbiol Infect Dis . 2024 May 9;109(3):116344.
[4]. Durlobactam, a Diazabicyclooctane β-Lactamase Inhibitor, Inhibits BlaC and Peptidoglycan Transpeptidases of Mycobacterium tubercul. ACS Infect Dis . 2024 May 10;10(5):1767-1779.
[5]. In vivo dose response and efficacy of the β-lactamase inhibitor, durlobactam, in combination with sulbactam against the Acinetobacter baumannii-calcoaceticus complex. Antimicrob Agents Chemother. 2024 Jan; 68(1): e00800-23.
[6]. The Pharmacokinetics/Pharmacodynamic Relationship of Durlobactam in Combination With Sulbactam in In Vitro and In Vivo Infection Model Systems Versus Acinetobacter baumannii-calcoaceticus Complex. Clin Infect Dis. 2023 May 1;76(Suppl 2):S202-S209.

Dulobactam belongs to the azabicycloalkyl group of compounds, with the chemical name (1R,2S,5R)-3-methyl-7-oxo-1,6-diazabicyclo[3.2.1]oct-3-en-2-carboxamide, in which the 6-amino hydrogen atom is replaced by a sulfonoxy group. It is an EC 3.5.2.6 (β-lactamase) inhibitor and antibacterial agent. It is a primary amide, azabicycloalkyl, hydroxylamine O-sulfonic acid, and monocarboxylic acid amide. It is the conjugate acid of dulobactam (1-). Dulobactam is a diazabicyclooctane non-β-lactamase inhibitor. It is often used in combination with sulbactam to prevent degradation by certain serine β-lactamases. The combination of dulobactam and sulbactam was first approved by the FDA in May 2023. It is used to treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible strains of the Acinetobacter baumannii-Calcium acetate complex. Dulobactam is a β-lactamase inhibitor. The mechanism of action of dulobactam is as a β-lactamase inhibitor. See also: Dulobactam sodium (active ingredient). Indications Dulobactam, in combination with sulbactam, is indicated for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults caused by susceptible strains of the Acinetobacter baumannii-Calcium acetate complex. Mechanism of Action Dulobactam is a diazabicyclooctane non-β-lactamase inhibitor. When used in combination with sulbactam, it protects sulbactam from degradation by certain serine β-lactamases. Dulobactam is carbamate-mediated at the active site of β-lactamases: the covalent bond between dulobactam and β-lactamases is reversible due to the recyclization of the ammonium sulfate group on dulobactam, indicating that dulobactam can exchange from one enzyme molecule to another, a process also known as acylation exchange.

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Pharmacodynamics
Compared to other β-lactamase inhibitors, dulobactam exhibits broader-spectrum activity, showing potent inhibition against serine β-lactamases of types A, C, and D. Dulobactam is inactive against type B metallo-β-lactamases, which are rare in clinical isolates of Acinetobacter baumannii. Dulobactam alone has no antibacterial activity against Acinetobacter baumannii-Calcium acetate complex isolates.

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- Dulobactam (ETX2514) is a diazabicyclooctane (DBO) class of β-lactamase inhibitors, unlike traditional inhibitors such as clavulanic acid. It has broad-spectrum activity against class A, C, and D β-lactamases, addressing a critical unmet need for treating infections caused by multidrug-resistant Gram-negative bacteria such as Acinetobacter baumannii, which are often resistant to multiple β-lactam antibiotics[1].
- Dulobactam (ETX2514) has been clinically developed with combination therapy with sulbactam, a β-lactam antibiotic. Sulbactam is intrinsically active against Acinetobacter baumannii but is inactivated by β-lactamases; dulobactam (ETX2514) restores the efficacy of sulbactam by inhibiting these resistant enzymes. This combination is particularly suitable for treating hospital-acquired infections (such as pneumonia and bloodstream infections) caused by carbapenem-resistant Acinetobacter baumannii[5]. Dulobactam (ETX2514) has a dual mechanism of action against Mycobacterium tuberculosis: it inhibits BlaC (which protects β-lactam antibiotics from degradation) and directly inhibits peptidoglycan transpeptidase (which disrupts cell wall synthesis). This dual activity makes it a potential candidate for combination therapy against drug-resistant tuberculosis, including strains resistant to isoniazid or rifampin [4]
- As of the date of publication, dulobactam (ETX2514) (in combination with sulbactam) has completed a Phase I clinical trial in healthy subjects, demonstrating good pharmacokinetic properties and safety. Phase II/III trials are currently underway to evaluate its efficacy in patients with Acinetobacter baumannii infection [2,6]

C8H11N3O6S

277.25

277.036

C, 34.66; H, 4.00; N, 15.16; O, 34.62; S, 11.56

1467829-71-5

1467829-71-5 (free acid);1467157-21-6 (sodium);

89851852

Solid powder

1.8±0.1 g/cm3

1.691

-2.53

2

6

3

18

536

2

C1(=C[C@@H]2C[N@@](C(N2OS(=O)(=O)O)=O)[C@@H]1C(N)=O)C

BISPBXFUKNXOQY-RITPCOANSA-N

InChI=1S/C8H11N3O6S/c1-4-2-5-3-10(6(4)7(9)12)8(13)11(5)17-18(14,15)16/h2,5-6H,3H2,1H3,(H2,9,12)(H,14,15,16)/t5-,6+/m1/s1

(1R,2S,5R)-2-carbamoyl-3-methyl-7-oxo-1,6-diazabicyclo[3.2.1]oct-3-en-6-yl hydrogen sulfate

ETX 2514ETX-2514 ETX2514 Durlobactam Durlobactam.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: > 10 mM

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)