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Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
Published on: July 24, 2021
New boronate drugs and evolving NDM-mediated beta-lactam resistance
Olga Lomovskaya1, Ruslan Tsivkovski1, Maxim Totrov2
1Qpex Biopharma, Inc. , San Diego, California, USA.
Abstract:
Taniborbactam and xeruborbactam are dual serine-/metallo-beta-lactamase inhibitors (BLIs) based on a cyclic boronic acid pharmacophore that undergo clinical development. Recent report demonstrated that New Delhi metallo-beta-lactamase (NDM)-9 (differs from NDM-1 by a single amino acid substitution, E152K, evolved to overcome Zn (II) deprivation) is resistant to inhibition by taniborbactam constituting pre-existing taniborbactam resistance mechanism. Using microbiological and biochemical experiments, we show that xeruborbactam is capable of inhibiting NDM-9 and propose the structural basis for differences between two BLIs.
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