ACHN-975 TFA is a selective LpxC inhibitor with subnanomolar inhibitory activity against a wide range of gram-negative bacteria, exhibiting low MIC values (≤1 μg/mL).

LpxC:

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 a MIC of ≤2?μg/ml. It against Pseudomonas aeruginosa with an MIC50 and MIC90 of 0.06 and 0.25?μg/ml, respectively. 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].

ACHN-975 TFA (i.p.; 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].

Animal Model: Neutropenic mouse thigh model with P. aeruginosa ATCC 27853. Dosage: 5-30 mg/kg. Administration: i.p.; single dose [2]