ACHN-975 is a highly potent and selective LpxC inhibitor, demonstrating subnanomolar inhibitory activity. It effectively targets a broad spectrum of gram-negative bacteria, with low minimum inhibitory concentration (MIC) values (≤1 μg/mL)[1].

ACHN-975 is effective against Enterobacteriaceae spp with an IC50 of 0.02 nM[1] and shows MIC90 values of 1, 0.5, and >64 μg/mL against Enterobacteriaceae spp, Pa, and Ab, respectively[1]. ACHN-975 is also active against six P. aeruginosa isolates, with MIC values of 0.12, 0.06, and 0.06 μg/mL for APAE1064, APAE1232, and APAE1064 isolates, respectively[2]. It exhibits MIC50 and MIC90 values of 0.06 and 0.25 μg/mL against Pseudomonas aeruginosa[2] and inhibits 100% of the tested P. aeruginosa isolates at an MIC of ≤2 μg/mL. LpxC, a highly conserved enzyme in gram-negative bacteria, catalyzes the first committed step of lipid A biosynthesis and is characterized as a Zinc-dependent metalloamidase UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase[1].

ACHN-975 (intraperitoneal administration; 5-30 mg/kg; single dose) causes a steady reduction in bacterial titers within the first 4 hours across all dosing groups, indicating that the level of free drug falls below the MIC for this isolate (0.25 μg/ml) by 2 hours after a 10 mg/kg dose and by 4 hours after a 30 mg/kg dose[2].