ACHN-975

ACHN-975 is a selective LpxC inhibitor and exhibits a subnanomolar LpxC inhibitory activity. ACHN-975 is against a wide range of gram-negative bacterias with low MIC values (≤1 μg/mL)^[1]. IC50 & Target: LpxC^[1] In Vitro: ACHN-975 is against Enterobacteriaceae spp with an IC₅₀ of 0.02 nM^[1].
ACHN-975 is against Enterobacteriaceae spp, Pa, and Ab with MIC90 values of 1, 0.5, and >64 μg/mL, respectively^[1].
ACHN-975 is potently against the?P. aeruginosa?isolates tested, inhibiting 100% of the isolates at an MIC of ≤2?μg/ml. It against?Pseudomonas aeruginosa?with an MIC₅₀?and MIC₉₀?of 0.06 and 0.25?μg/ml, respectively^[2].
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].
LpxC is highly conserved in gram-negative bacteria and catalyzes the first committed step of lipid A biosynthesis. LpxC is the bacterial enzyme Zinc-dependent metalloamidase UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase^[1].
In Vivo: 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. The sampling 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].