VNRX-6958

VNRX-6958 is a preclinical, non-β-lactam antibacterial small molecule discovered by Venatorx Pharmaceuticals as a **cyclic benzo-oxaborinine penicillin‑binding protein inhibitor** targeting multidrug‑resistant Neisseria gonorrhoeae. It is a selective, reversible covalent inhibitor of the transpeptidase activity of penicillin‑binding protein 2 (PBP2), designed to overcome both β‑lactamase‑mediated and PBP2‑mediated resistance and to remain impervious to β‑lactamase hydrolysis.[1] Structure–activity optimization around a benzo‑oxaborinine scaffold and a mezlocillin‑inspired imidazolinone ureido “head group” yielded VNRX‑6958 with improved PBP2 binding (including mosaic PBP2 from ceftriaxone‑resistant strains) and potent in vitro activity against wild‑type and multidrug‑resistant N. gonorrhoeae, along with favorable mouse pharmacokinetics after subcutaneous dosing, robust efficacy in a murine genital gonorrhea model, and a favorable in vitro safety and ADMET profile.[1]