生物活性

• 描述Enoyl-ACP (acyl carrier protein) reductase is known to have four distinct enzyme forms: FabI, FabK, FabL, and FabV. FabI is the sole form of enoyl-ACP reductase present in Staphylococcus aureus, Staphylococcus epidermidis, and a few other bacterial species. FabI is an essential enzyme that catalyzes the reduction of trans-2-enoyl-acyl carrier protein (trans-2-enoyl-ACP) to acyl-ACP, the final step in each elongation cycle of bacterial fatty acid biosynthesis. AFN-1252 is an investigational inhibitor of staphylococcal FabI. It inhibited all clinical isolates of Staphylococcus aureus (n = 502) and Staphylococcus epidermidis (n = 51) tested, including methicillin (meticillin)-resistant isolates, at concentrations of ≤0.12 μg/ml. AFN-1252 was tested over a doubling-dilution concentration range of 0.008 to 4 μg/ml, and its MICs were recorded following 20 to 24 h of incubation at 35°C in ambient air. For the reference strain S. aureus ATCC 29213, AFN-1252 reproducibly demonstrated an MIC of 0.015 μg/ml. AFN-1252 demonstrated MIC₉₀s for methicillin-resistant S. aureus and S. epidermidis and multidrug-resistant S. aureus and S. epidermidis of ≤0.008 μg/ml^[2]. Abscesses were formed on the flanks of female CD-1 mice by the injection of 10⁵ CFU of an S. aureus (MRSA) culture mixed with Cytodex (dextran) beads. AFN-1252, administered orally at 100, 30 or 10 mg/kg, demonstrated log reductions of 5.9, 5.2 and 2.5 CFU when administered bid and 5.2, 4.1 and 2.4 CFU when dosed qd, respectively, as compared to the vehicle treated control animals^[3].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01519492	Skin and Subcutaneous Tissue B... more >>acterial Infections Wound Infection Cutaneous Abscess Burn Infection Cellulitis Collapse <<	Phase 2	Completed	-	United States, California ... more >> SITE 018 Buena Park, California, United States, 90620 SITE 005 Chula Vista, California, United States, 91911 SITE 001 La Mesa, California, United States, 91942 SITE 016 Oceanside, California, United States, 92056 United States, Georgia SITE 017 Augusta, Georgia, United States, 30909 SITE 002 Columbus, Georgia, United States, 31904 SITE 004 Savannah, Georgia, United States, 31406 United States, Nevada SITE 006 Las Vegas, Nevada, United States, 89109 United States, New Jersey SITE 003 Somers Point, New Jersey, United States, 08244 United States, Ohio SITE 007 Cincinnati, Ohio, United States, 45267 SITE 011 Toledo, Ohio, United States, 43608 United States, Tennessee SITE 008 Nashville, Tennessee, United States, 37232 Canada, Alberta SITE 014 Edmonton, Alberta, Canada, T6G 2B7 Canada, Ontario SITE 015 Kingston, Ontario, Canada, K7L 2V7 Collapse <<

• 参考文献

• [1] Parsons JB, Kukula M, et al. Perturbation of Staphylococcus aureus gene expression by the enoyl-acyl carrier protein reductase inhibitor AFN-1252. Antimicrob Agents Chemother. 2013 May;57(5):2182-90.

  [2] AFN-1252, a FabI inhibitor, demonstrates a Staphylococcus-specific spectrum of activity

  [3] Efficacy of AFN-1252 and Vancomycin in the Mouse Subcutaneous Abscess Model with a Methicillin-Resistant S. aureus