Recent advances in the preclinical evaluation of the topical antibacterial agent REP8839.
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.
Critchley
Ian A
IA
Microbiology Research, Replidyne, Inc., 1450 Infinite Drive, Louisville, CO 80027, USA. icritchley@replidyne.com
Ochsner
Urs A
UA
D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D003959:Diamines / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D024881:Drug Resistance, Bacterial / Q000235:genetics; D006801:Humans; D008718:Methionine-tRNA Ligase / Q000037:antagonists & inhibitors / Q000235:genetics; D013876:Thiophenes / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D003959:Diamines; C533960:REP8839; D013876:Thiophenes; D008718:Methionine-tRNA Ligase