Vaborbactam is a non-β-lactam β-lactamase inhibitor. It is synthetic biochemical based on a a cyclic boronic acid pharmacophore. It was discovered by Rempex Pharmaceuticals, a subsidiary of The Medicines Company. It can increase the potency of antibiotics by inhibiting the bacterial β-lactamase enzymes that would otherwise degrade them. In particular, it has a high affinity for serine β-lactamases. Thus, it is often used in combination with a carbapenem (ie meropenem, biapenem).
Relebactam is sparingly soluble in DMSO and DMF.
| Molecular Formula | C12H16BNO5S |
| Spectrum | Vaborbactam is a broad-spectrum inhibitor. Although not an antibiotic itself, when used in combination with meropenem (ie meropenem/vaborbactam) it can be used against Gram-negative bacteria such as Klebsiella pneumoniae carbapenemase (KPC) in a concentration-dependent fashion. When in combination with biapenem, it potentiates its activity against K. pneumoniae. |
| Mechanism of Action |
Vaborbactam shows no antibacterial activity alone. It inhibits bacterial β-lactamases and thus can restore the activity of antibacterial agents. It has a specific affinity for Ambler class A and C enzyme such as serine β-lactamases. If used in combination with meropenem, it doesn't negatively interfere with the antibiotic activity of meropenem. It interacts with beta-lactamases via precovalent and covalent binding. |
| Microbiology Applications |
Vaborbactam a high high affinity for serine β-lactamases, with an IC50 >1 mM against a panel of mammalian human serine hydrolases (Hecker et al, 2015). |
| References |
Bush K (2018) Game changers: New β-Lactamase inhibitor combinations targeting antibiotic resistance in Gram-negative bacteria. ACS Infect.Dis. 24(2):84-87 PMID 29232103 Griffith DC, Loutit JS, Morgan EE, Durso S, Dudley MN (2016) Phase 1 study of the safety, tolerability, and pharmacokinetics of the β-lactamase inhibitor Vaborbactam (RPX7009) in healthy adult subjects. Antimicrob Agents Chemother. 60(10):6326-6332. PMID 27527080 Hecker SJ et al (2015) Discovery of a cyclic boronic acid β-Lactamase inhibitor (RPX7009) with utility vs class A serine carbapenemases. J. Med. Chem. 58(9):3682-3692. PMID 25782055 |