Disease relevance of U-100592

• Oxazolidinone-resistant mutants of Staphylococcus aureus, isolated with a spiral plating technique, had a 16-fold higher MIC (2 versus 32 microg/ml) of eperezolid when compared to the parental sensitive strain [1].
• Eperezolid binds specifically to the 50S ribosomal subunit of Escherichia coli [2].
• Activities of the oxazolidinones linezolid and eperezolid in experimental intra-abdominal abscess due to Enterococcus faecalis or vancomycin-resistant Enterococcus faecium [3].
• The in vitro activity values (MICs) of linezolid, eperezolid, and comparator antibiotics against 102 strains of Rhodococcus equi isolated from humans and animals were determined [4].
• In several mouse models of methicillin-resistant Staphylococcus aureus infection, U-100592 and U-100766 yielded oral 50% effective doses (ED50) ranging from 1.9 to 8.0 mg/kg of body weight, which compared favorably with vancomycin subcutaneous ED50 values of 1.1 to 4.4 mg/kg [5].

High impact information on U-100592

• PNU-177553 and eperezolid were found to bind only to the 50S subunit, with similar affinity as to the 70S ribosome, and to have no affinity for the 30S subunit [6].
• Ribosomes from an oxazolidinone-resistant mutant confer resistance to eperezolid in a Staphylococcus aureus cell-free transcription-translation assay [1].
• Important representatives of this class include the morpholine derivative linezolid 2, which is currently in phase III clinical trials, and the piperazine derivative eperezolid 3 [7].
• We evaluated the in vitro activities of clinafloxacin, CL331,002, LY333328, quinupristin dalfopristin, and eperezolid (formerly known as U-100,592) against four strains of enterococci [8].
• The binding of eperezolid to the ribosome is competitively inhibited by chloramphenicol and lincomycin [2].

Chemical compound and disease context of U-100592

• Both linezolid and eperezolid were potent inhibitors of cell-free transcription-translation in E. coli, exhibiting 50% inhibitory concentrations (IC50s) of 1.8 and 2.5 microM, respectively [9].
• The MIC90 of U-100592 and U-100766 for oxacillin-resistant Staphylococcus aureus was 2 micrograms/ml, the same as observed for oxacillin-susceptible strains [10].

Biological context of U-100592

• For eperezolid, 128 microg of RNA per ml produced an IC50 of 50 microM whereas a concentration of 32 microg/ml yielded an IC50 of 20 microM [9].
• The group mean platelet count was slightly decreased for most PNU-100592-treated groups [11].
• PNU-100592 may be useful in the study of the regulation of endomitosis during megakaryocytopoiesis in the dog [11].

Anatomical context of U-100592

• The specific binding of eperezolid is dose dependent and is proportional to the ribosome concentrations [2].
• U-100592 MICs for 7 of 230 strains (2 from blood, 3 from middle-ear fluid, and 2 from the upper respiratory tract) were 1 microgram/ml [12].
• Hypersegmented megakaryocytes and megakaryocytes with multiple separate nuclei in dogs treated with PNU-100592, an oxazolidinone antibiotic [11].

Associations of U-100592 with other chemical compounds

• The comparative in vitro activities of two new oxazolidinone antimicrobial agents, U-100592 and U-100766, against 180 isolates of enterococci representing several resistance profiles were examined by using an agar dilution technique [13].

Gene context of U-100592

• The results demonstrated that the sera from most human subjects dosed with eperezolid or linezolid were inhibitory to S. aureus and E. faecalis and S. pneumoniae and that many of the samples exhibited bactericidal activity for S. pneumoniae [14].
• In vitroActivity of Linezolid and Eperezolid, Two Novel Oxazolidinone Antimicrobial Agents, Against Anaerobic Bacteria [15].

Analytical, diagnostic and therapeutic context of U-100592

• Simple method for the assay of eperezolid in brain heart infusion broth by high-performance liquid chromatography [16].

References