AFN-1252 is an inhibitor of staphylococcal enoyl-acyl carrier protein reductase (FabI; Ki = 12.8 nM), an enzyme that activates bacterial fatty acid biosynthesis. It is selective for isolates of methicillin-susceptible and methicillin-resistant S. aureus (MIC90s = ≤0.008 μg/ml) over isolates of S. pneumoniae, β-hemolytic streptococci, Enterococcus, Enterobacteriaceae, non-fermentative Gram-negative bacilli, and M. catarrhalis (MIC90s = >4 μg/ml). In vivo, AFN-1252 increases survival in a murine acute lethal septicemia model, showing 100% survival when administered at a single oral dose of 1 mg/kg.
