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OSUAB-0284 (284) is a novel, small-molecule anti-staphylococcal agent targeting bacterial type II topoisomerases. 284 inhibited supercoiling by DNA gyrase and decatenation by topoisomerase IV with similar (balanced) potency (IC\n                      <jats:sub>50<\/jats:sub>\n                      values of 0.80 and 0.15 \u03bcM, respectively) and promoted the accumulation of single-strand DNA breaks mediated by DNA gyrase and topoisomerase IV. Cryo-electron microscopy of 284 in ternary complex with 20-bp DNA and\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      DNA gyrase elucidated the binding mode. 284 displayed impressive activity against a panel of 100 recent clinical isolates of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      , with a minimal inhibitory concentration (MIC\n                      <jats:sub>90<\/jats:sub>\n                      ) of 0.25 \u03bcg\/mL. Spontaneous frequency of resistance studies indicated a very low rate of resistance selection (&lt;9.62 \u00d7 10\n                      <jats:sup>\u221210<\/jats:sup>\n                      ).\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      studies of absorption, distribution, metabolism, excretion, and toxicity and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      pharmacokinetics studies in mice and rats revealed favorable properties for further development. 284 was efficacious in a thigh infection model using neutropenic mice, with twice-daily oral doses \u226550 mg\/kg demonstrating ~1 log\n                      <jats:sub>10<\/jats:sub>\n                      reduction in bacterial colony-forming units. Preliminary safety studies in rats demonstrated that 284 was well tolerated up to the highest tested oral dose of 1,000 mg\/kg. 284 is currently in preclinical development as a novel anti-staphylococcal therapy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00698-26","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:35:28Z","timestamp":1792676128000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>In vitro<\/i>\n                    and\n                    <i>in vivo<\/i>\n                    activity of OSUAB-0284, a preclinical candidate for\n                    <i>Staphylococcus aureus<\/i>\n                    infections"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7378-4416","authenticated-orcid":true,"given":"Chelsea 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