G0775

G0775 is a synthetic, small molecule antibiotic developed by Genentech as an optimized derivative of the arylomycin natural product class. It targets the essential bacterial enzyme type I signal peptidase (SPase), which is responsible for removing signal peptides from proteins translocated across the cytoplasmic membrane. G0775 utilizes a novel covalent mechanism of action, where an aminoacetonitrile electrophilic warhead binds to the Lys146 residue of the enzyme. This compound exhibits potent, broad-spectrum activity against multidrug-resistant (MDR) Gram-negative bacteria, including the ESKAPE pathogens *Escherichia coli*, *Klebsiella pneumoniae*, *Pseudomonas aeruginosa*, and *Acinetobacter baumannii*. Notably, G0775 bypasses traditional resistance mechanisms by penetrating the bacterial outer membrane through a porin-independent mechanism and is significantly more potent than naturally occurring arylomycins.

Other names

arylomycin derivative