AFN-1252: Enoyl-[acyl-carrier-protein] reductase [NADH] FabI inhibitor Antibacterial agent

摘要

Since it's first appearance in hospitals in 1960, methicillin-resistant Staphylococcus aureus (MRSA) has become a rising cause of morbidity, mortality and healthcare costs. AFN-1252 is an oral, small molecule in a new class of antibiotics based on enoyl-[acyl-carrier-protein] reductase [NADH] FabI inhibition which is in phase II clinical trials for the treatment of MRSA infections at Debiopharm. In in vitro studies, AFN-1252 showed potent and selective inhibition of S. aureus FabI, and potent activity against MRSA clinical isolates, with no cross resistance to other antimicrobials. In murine models of staphylococcal infection, it showed an improved activity in comparison with linezolid or vancomycin. In a phase II clinical trial, AFN-1252 (200 mg twice daily) in 103 patients with acute bacterial skin and skin structure infections (ABSSSIs) due to staphylococci showed a clinical success rate of 93.4%, with treatment-emergent adverse events mild to moderate in severity.