The University of Washington and TSRL, Inc. are developing first-in-class small molecule antibacterials with excellent oral bioavailability and efficacy in in vivo S. aureus infection models.
Orally available tRNA Synthase Inhibitors as a differentiated treatment for methicillin-resistant staphylococcus aureus infection
MRS-2541 is a novel lead candidate antibiotic targeting Gram+ bacteria by a new mechanism of action. MRS-2541 inhibits bacterial methionyl-tRNA synthetase required for bacterial protein synthesis, which is very different from its mammalian counterpart. MRS-2541 is the result of an arduous testing cascade of over 500 compounds requiring broad-spectrum in vitro and in vivo Gram+ activity, a low resistance frequency and minimal hERG and mitochondrial toxicity.
The initial clinical indication will be acute bacterial skin and skin structure infections (ABSSSI) with clear endpoints and relatively easy enrollments. MRS-2541 is highly potent against serious pathogens such as methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus faecium (VRE), and Streptococcus species, with minimum inhibitory concentrations (MICs) ≤ 0.5 µg/mL, which are below those of widely used drugs such as vancomycin and linezolid. MRS-2541 has minimal cytotoxicity on mammalian cells, is well tolerated in mice at 150 mg/Kg/day, has excellent oral bioavailability, and is as efficacious as linezolid in the S. aureus and S. pyogenes thigh murine models of infection by both the oral and subcutaneous route.
The project has been supported by $6.6M in non-dilutive funding to date.
