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

ACHN-975 (intraperitoneal administration; 5-30?mg/kg; single dose) leads to a steady reduction in bacterial titers in the first 4?h following treatment for all dosing groups, which shows that the level of free drug in this model drops below the ACHN-975 MIC for this isolate (0.25?μg/ml) by 2?h after treatment with the 10 mg/kg dose and by 4?h after treatment with the 30 mg/kg dose[2].