oral prodrug of serine _-lactamase inh.
in dev. for multidrug resistant bact. infection
from optimization of prior _-lactamase inh.
J. Med. Chem., Jul. 24, 2020
Entasis Therapeutics, Waltham, MA
ETX0282 is an oral prodrug of a class A, C, and D serine β-lactamase inhibitor in clinical development for drug-resistant enterobacterial infections in combination with the beta-lactam drug cefpodoxime proxetil. Impressively ETX0282 had no observed adverse effect levels (NOAELs) of 500 mg/kg/day and 400 mg/kg/day in rat and dog, respectively, despite the reactive-looking nature of the strained bridged carbamate core and the monofluoroether. I was surprised by the chemical stability of the fluoroether moiety, which can be seen in the co-crystal structure.