Vaborbactam targets serine β-lactamases, enzymes produced by bacteria that hydrolyze β-lactam antibiotics and confer resistance. Vaborbactam is a cyclic boronic acid-based inhibitor that forms a reversible covalent complex with the active-site serine of β-lactamases. It is active against class A (including extended-spectrum β-lactamases, ESBLs) and class C (AmpC) β-lactamases. By inhibiting these enzymes, vaborbactam protects co-administered β-lactam antibiotics (such as meropenem) from degradation.

Vaborbactam exhibits a wide range of β-lactamase inhibition, with a strong affinity for KPC, CTX-M, SHV, and CMY enzymes[1]. When the concentration of the inhibitor is fixed at ≥8 μg/mL, maximum potentiation is achieved (≥96.5% of isolates are inhibited at ≤2 μg/mL of SM 7338-vaborbactam). Vaborbactam restores SM 7338 activity for 72.7 to 98.1% of CPE isolates at ≤2 μg/mL. At a fixed concentration of 8 μg/mL, SM 7338-vaborbactam inhibits 93.7% of CPE isolates that show elevated SM 7338 MICs at ≤1 μg/mL (MIC50, ≤0.06 μg/mL for all organisms)[2]. Vaborbactam functions as a competitive inhibitor and prevents the b-lactamase from hydrolyzing it by creating a reversible dative bond with the blactamase[3].

---

In vitro, vaborbactam demonstrates potent inhibition of class A and class C serine β-lactamases. It shows minimal inhibitory activity against class D β-lactamases and is not active against metallo-β-lactamases. The compound has been characterized in enzyme inhibition assays measuring the hydrolysis of chromogenic or fluorogenic β-lactam substrates. Specific IC50 values for various β-lactamases are not detailed in the available sources.

Vaborbactam (RPX-7009; MP-7009) is well tolerated and has a half-life of 1.23 h, and steadystate volume of distribution of 21.0 L in subjects[3].

---

In vivo, vaborbactam is administered intravenously in combination with meropenem. The combination has demonstrated efficacy in clinical trials for the treatment of complicated urinary tract infections and other infections caused by carbapenem-resistant Enterobacteriaceae (CRE). The compound is approved by the FDA for this indication. Specific animal model data are not detailed in the available sources.

The β-lactamase inhibition assay for vaborbactam involves incubating the compound with a recombinant β-lactamase enzyme and a chromogenic or fluorogenic β-lactam substrate (such as nitrocefin). The reaction is carried out in a buffer optimized for the enzyme. The hydrolysis of the substrate produces a colorimetric or fluorescent signal that is measured over time. The IC50 for inhibition of substrate hydrolysis is calculated. Selectivity is assessed by testing against a panel of β-lactamases.

To evaluate the antibacterial activity of vaborbactam in combination with meropenem, bacterial strains expressing β-lactamases are cultured in cation-adjusted Mueller-Hinton broth. Two-fold serial dilutions of meropenem alone and in combination with a fixed concentration of vaborbactam are prepared in 96-well plates. Bacterial suspensions are added, and plates are incubated at 35-37°C for 18-24 hours. The MIC of meropenem is determined, and the fold-reduction in MIC in the presence of vaborbactam is calculated.

The in vivo efficacy of vaborbactam in combination with meropenem is evaluated in mouse models of bacterial infection, such as the thigh infection model or peritonitis model. Immunocompetent or neutropenic mice are infected with a β-lactamase-producing bacterial strain. Vaborbactam and meropenem are administered intravenously at various doses. At the end of the treatment period, animals are euthanized, and target tissues are collected. The bacterial load is determined by homogenizing the tissue and plating serial dilutions on agar plates to count CFU.

Absorption, Distribution and Excretion
The peak plasma concentration (Cmax) and AUC of vaborbactam increase dose-proportionally. In healthy adult subjects, after multiple 3-hour intravenous infusions of 2 g, Cmax was 55.6 mg/L and AUC was 588 mg·h/L. In patients using the same dosing regimen, steady-state Cmax was 71.3 mg/L and AUC was 835 mg·h/L. Repeated dosing is not expected to change vaborbactam exposure (expressed as Cmax and AUC), and no accumulation of vaborbactam in plasma was observed in repeated-dose studies. Vaborbactam is primarily excreted by the kidneys, with approximately 75% to 95% of the dose excreted unchanged in the urine over 24 to 48 hours. The steady-state volume of distribution of vaborbactam in patients is 18.6 L. The mean renal clearance of vaborbactam is 8.9 L/h. The mean non-renal clearance of vaborbactam is 2.0 L/h, indicating that vaborbactam is almost completely cleared via the renal route. In healthy subjects, the clearance of vaborbactam was 10.9 L/h after multiple 3-hour intravenous infusions of 2 g dose. In patients, the clearance of vaborbactam was 7.95 L/h after a 3-hour intravenous infusion of 2 g dose.
Metabolism/Metabolites
Vaborbactam is not metabolized.
Biological Half-Life
In healthy subjects, the half-life of vaborbactam was 1.68 hours after multiple 3-hour intravenous infusions of 2 g dose. After a 3-hour intravenous infusion of 2 g dose, the half-life of vaborbactam was 2.25 hours.

---

Vaborbactam is administered intravenously in combination with meropenem. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, half-life, AUC) for vaborbactam are not detailed in the available sources. The compound has a molecular weight of 297.13 and a molecular formula of C12H16BNO5S. It is formulated as a lyophilized powder for intravenous administration in combination with meropenem.

Protein Binding
The average serum protein binding rate of vaborbactam is approximately 33%.

---

Vaborbactam is generally well-tolerated, with common adverse effects including headache, infusion site reactions, and diarrhea. As a β-lactamase inhibitor, it is used in combination with meropenem, and the safety profile reflects the combination. The compound is approved by the FDA for the treatment of complicated urinary tract infections. Specific toxicity data from preclinical studies are not detailed in the available sources.

[1]. Discovery of a Cyclic Boronic Acid β-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases. J Med Chem. 2015 May 14;58(9):3682-92.

[2]. Effect of the β-Lactamase Inhibitor Vaborbactam Combined with SM 7338 against Serine Carbapenemase-Producing Enterobacteriaceae. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5454-8.

[3]. Novel Beta-Lactamase Inhibitors: Unlocking Their Potential in Therapy.

Vaborbactam is a β-lactamase inhibitor based on a cyclic borate pharmacophore. It was previously used in clinical trials to investigate bacterial infections in patients with varying degrees of renal impairment. In August 2017, a combination antimicrobial drug called Vaboromere was approved by the FDA for the treatment of complicated urinary tract infections (cUTI) in adults. Vaboromere consists of vaborbactam and meropenem and is administered intravenously. The addition of vaborbactam aims to reduce meropenem degradation by inhibiting serine β-lactamases expressed by the target microorganism. The goal of this therapy is to alleviate infection-related symptoms of cUTI and achieve negative urine culture results in cases where infection is confirmed or highly suspected to be caused by susceptible bacteria. Vaborbactam is a β-lactamase inhibitor. The mechanism of action of vaborbactam is as a β-lactamase inhibitor.

---

Drug Indications
Used in combination with meropenem for the treatment of complicated urinary tract infections (cUTI) in patients aged 18 years and older, including pyelonephritis caused by susceptible microorganisms such as Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae complex.

FDA Label

Treatment of Gram-negative bacterial infectionsMechanism of Action
vaborbactam is a cyclic borate pharmacophore β-lactamase inhibitor that potently inhibits Klebsiella pneumoniae carbapenemase (KPC) and other Ambler class A and C enzymes, such as resistant serine β-lactamases. Commonly used antibiotics include carbapenems. Vaborbactam is a potent class A carbapenemase inhibitor, such as KPC, and also an inhibitor of other class A (CTX-M, SHV, TEM) and class C (P99, MIR, FOX) β-lactamases.
Vaborbactam interacts with Ambler class A and C β-lactamases via pre- and covalent binding. It does not inhibit class D or B carbapenemases. Novel β-lactamases produced by bacterial isolates accelerate the degradation of β-lactam antibiotics, reducing their clinical efficacy and posing challenges to patients receiving standard antibiotic therapy. When used in combination with meropenem, vaborbactam acts as a non-suicidal β-lactamase inhibitor, protecting meropenem from degradation mediated by serine β-lactamases, such as Klebsiella pneumoniae carbapenemase (KPC).

---

Pharmacodynamics
Vaborbactam alone has no antibacterial activity; it restores the antibacterial activity of other antimicrobial drugs (such as meropenem) by inhibiting serine β-lactamases in certain microorganisms, thus slowing the degradation of these drugs. Vaborbactam does not reduce the activity of meropenem against meropenem-sensitive bacteria. Vaborbactam, when used in combination with meropenem (a penem antibiotic), enhances the bactericidal activity of meropenem against carbapenem-resistant KPC Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae in a concentration-dependent manner. In certain animal models of infection with KPC-producing Enterobacteriaceae that are insensitive to meropenem, Vaborbactam restores the antibacterial activity of meropenem.

---

Vaborbactam is a novel, non-β-lactam β-lactamase inhibitor active against class A and class C serine β-lactamases. It is approved in combination with meropenem (as Vabomere) for the treatment of complicated urinary tract infections, including pyelonephritis, caused by susceptible Enterobacteriaceae. The compound is a cyclic boronic acid-based inhibitor that forms a reversible covalent complex with the active-site serine of β-lactamases.

C12H16BNO5S

297.13

297.084

C, 48.51; H, 5.43; B, 3.64; N, 4.71; O, 26.92; S, 10.79

1360457-46-0

56649692

Light brown to yellow solid powder

1.4±0.1 g/cm3

1.572

3

6

5

20

370

2

S1C([H])=C([H])C([H])=C1C([H])([H])C(N([H])[C@]1([H])B(O[H])O[C@]([H])(C([H])([H])C(=O)O[H])C([H])([H])C1([H])[H])=O

IOOWNWLVCOUUEX-WPRPVWTQSA-N

InChI=1S/C12H16BNO5S/c15-11(7-9-2-1-5-20-9)14-10-4-3-8(6-12(16)17)19-13(10)18/h1-2,5,8,10,18H,3-4,6-7H2,(H,14,15)(H,16,17)/t8-,10-/m0/s1

2-((3R,6S)-2-hydroxy-3-(2-(thiophen-2-yl)acetamido)-1,2-oxaborinan-6-yl)acetic acid

RPX-7009; MP-7009; RPX7009; MP7009; REBO07; REBO 07; MP7; MP 7; RPX 7009; MP 7009; REBO-07; MP-7; Trade name: Vabomere

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)

H2O : ~5.26 mg/mL (~17.70 mM)

Solubility in Formulation 1: 25 mg/mL (84.14 mM) in 108 mM sodium carbonate (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

---

Solubility in Formulation 2: ≥ 2.62 mg/mL (8.82 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.62 mg/mL (8.82 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
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.

---

Solubility in Formulation 4: 27.5 mg/mL (92.55 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

---

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