This property enables them to function as transition state analogs of serine carbapenemase-catalyzed lactam hydrolysis and thereby inhibit these enzymes.

[2] Carbapenemases can be broadly divided into two different categories based on the mechanism they use to hydrolyze the lactam ring in their substrates: Metallo-β-lactamases contain bound zinc ions in their active sites and are therefore inhibited by chelating agents like EDTA, while serine carbapenemases feature an active site serine that participates in the hydrolysis of the substrate.

[6][7] Given their mechanism of action, the possibility of off-target effects brought about through inhibition of endogenous serine hydrolases is an obvious possible concern in the development of boronic acid β-lactamase inhibitors, and in fact boronic acids like bortezomib have previously been investigated or developed as inhibitors of various human proteases.

[2] Consistent with its high in vitro specificity, vaborbactam exhibited a good safety profile in human phase I clinical trials, with similar adverse events observed in both placebo and treatment groups.

[8] Hecker et al. argue this specificity results from the higher affinity of human proteases to linear molecules; thus it is expected that a boron heterocycle will have zero effect on them.