Vaborbactam

Chemical Identity

Property	Value
Chemical Formula	C12H16BNO5S
Molecular Weight	297.13 Da
CAS Number	1360457-46-0
Peptide Class	Boronic Acid Derivative
Type	Cyclic boronate beta-lactamase inhibitor

Structure

Vaborbactam is a boronic acid-based inhibitor featuring a cyclic boronate pharmacophore that mimics the tetrahedral transition state of beta-lactam hydrolysis. The boronic acid forms a reversible covalent bond with the active site serine of beta-lactamases. A thiophene ring and sulfonamide group provide selectivity and potency.

Mechanism of Action

Vaborbactam inhibits class A and class C beta-lactamases, with exceptional potency against KPC (Klebsiella pneumoniae carbapenemase). The boronate forms a tetrahedral adduct with the catalytic serine, mimicking the transition state of beta-lactam hydrolysis. This restores meropenem activity against KPC-producing organisms.

Clinical Applications

• Complicated UTIs: Including pyelonephritis (FDA-approved indication)
• CRE infections: KPC-producing Enterobacterales
• Carbapenem-resistant infections: When combined with meropenem
• Hospital-acquired pneumonia: Off-label use

Pharmacokinetics

• Half-life: 1.5-2 hours (similar to meropenem)
• Protein binding: 33%
• Elimination: Renal (75-95% unchanged)
• Dosing: 4g/4g meropenem-vaborbactam IV every 8 hours
• Route: IV infusion over 3 hours

Safety and Side Effects

Headache, diarrhea, nausea, phlebitis, hypokalemia, and Clostridioides difficile infection. Generally well-tolerated with a safety profile similar to meropenem alone.

References

• Hecker, S.J., et al. (2015). Vaborbactam: a boronic acid beta-lactamase inhibitor. Journal of Medicinal Chemistry, 58, 3682-3692.
• Wunderink, R.G., et al. (2018). Meropenem-vaborbactam for CRE infections. New England Journal of Medicine, 378, 2387-2398.