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Recent advances in the preclinical evaluation of the topical antibacterial agent REP8839.
Current opinion in chemical biology 2008 Jul 9; In press
Critchley I IA, Ochsner U UA
Microbiology Research, Replidyne, Inc., 1450 Infinite Drive, Louisville, CO 80027, United States.
REP8839 is a synthetic fluorovinylthiophene-containing diaryldiamine that inhibits bacterial methionyl tRNA synthetase (MetRS) and is a new chemical entity that represents a novel pharmacological class. The compound has potent in vitro antibacterial activity against many clinically important Gram-positive bacteria including the major skin pathogens Staphylococcus aureus and Streptococcus pyogenes. In light of the emergence of methicillin-resistant S. aureus in the community and increasing resistance to mupirocin, REP8839 is being evaluated as a topical agent for the treatment of superficial skin infections. REP8839 was active against resistant phenotypes of S. aureus and can be formulated at high concentrations to minimize the development of resistance. A formulation of REP8839 has demonstrated efficacy in a porcine partial thickness wound infection model against mupirocin-resistant S. aureus.
Keywords: antibacterial REP8839 Gram-positive Staphylococcus aureus