MUT056399 (Fab-001)

MUT056399 is a highly potent inhibitor of the FabI enzyme of both S. aureus and E. coli with 50% inhibitory concentration IC50s of 12 nM and 58 nM, respectively. IC50 value: 12 nM (for S. aureus), 58 nM (for E. coli) [1]Target: FabI enzymein vitro: MUT056399 is a highly potent new inhibitor of the FabI enzyme of both Staphylococcus aureus and Escherichia coli. MUT056399 is very active against S. aureus strains, including methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), linezolid-resistant, and multidrug-resistant strains, with MIC90s between 0.03 and 0.12 μg/ml. MUT056399 is also active against coagulase-negative staphylococci, with MIC90s between 0.12 and 4 μg/ml. MUT056399 is very active against the 118 S. aureus strains tested, including MSSA and MRSA isolates and linezolid-resistant and multidrug-resistant strains, with MIC90s between ≤0.03 and 0.12 μg/ml.In vivo: MUT056399, administered subcutaneously, protected mice from a lethal systemic infection induced by MSSA, MRSA, and vancomycin-intermediate S. aureus strains (50% effective doses ranging from 19.3 mg/kg/day to 49.6 mg/kg/day). In the nonneutropenic murine thigh infection model, the same treatment with MUT056399 reduced the bacterial multiplication of MSSA and MRSA in the thighs of immunocompetent mice.

[1]. Escaich S, et al. The MUT056399 inhibitor of FabI is a new antistaphylococcal compound. Antimicrob Agents Chemother. 2011 Oct;55(10):4692-7. [2]. Schiebel J, et al. An ordered water channel in Staphylococcus aureus FabI: unraveling the mechanism of substrate recognitionand reduction. Biochemistry. 2015 Mar 17;54(10):1943-55.