{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:49:56Z","timestamp":1785307796424,"version":"3.55.0"},"reference-count":25,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bill &amp; Melinda Gates Foundation"},{"name":"GHDDI sponsors in Beijing, China"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Pleuromutilins are a group of antibiotics derived from the naturally occurring compound. The recent approval of lefamulin for both intravenous and oral doses in humans to treat community-acquired bacterial pneumonia has prompted investigations in modifying the structure to broaden the antibacterial spectrum, enhance the activity, and improve the pharmacokinetic properties. AN11251 is a C(14)-functionalized pleuromutilin with a boron-containing heterocycle substructure. It was demonstrated to be an anti-Wolbachia agent with therapeutic potential for Onchocerciasis and lymphatic filariasis. Here, the in vitro and in vivo PK parameters of AN11251 were measured including PPB, intrinsic clearance, half-life, systemic clearance, and volume of distribution. The results indicate that the benzoxaborole-modified pleuromutilin possesses good ADME and PK properties. AN11251 has potent activities against the Gram-positive bacterial pathogens tested, including various drug-resistant strains, and against the slow-growing mycobacterial species. Finally, we employed PK\/PD modeling to predict the human dose for treatment of disease caused by Wolbachia, Gram-positive bacteria, or Mycobacterium tuberculosis, which might facilitate the further development of AN11251.<\/jats:p>","DOI":"10.3390\/molecules28124628","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T02:02:28Z","timestamp":1686189748000},"page":"4628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Assessing Boron-Pleuromutilin AN11251 for the Development of Antibacterial Agents"],"prefix":"10.3390","volume":"28","author":[{"given":"Ming-Jie","family":"Han","sequence":"first","affiliation":[{"name":"Department of DMPK & Tox, Global Health Drug Discovery Institute, Zhongguancun Dongsheng International Science Park, Beijing 100192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of TB Biology, Global Health Drug Discovery Institute, Zhongguancun Dongsheng International Science Park, Beijing 100192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genhui","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of TB Biology, Global Health Drug Discovery Institute, Zhongguancun Dongsheng International Science Park, Beijing 100192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of TB Biology, Global Health Drug Discovery Institute, Zhongguancun Dongsheng International Science Park, Beijing 100192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6678-3293","authenticated-orcid":false,"given":"Shawn","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of TB Biology, Global Health Drug Discovery Institute, Zhongguancun Dongsheng International Science Park, Beijing 100192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyang","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of DMPK & Tox, Global Health Drug Discovery Institute, Zhongguancun Dongsheng International Science Park, Beijing 100192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1073\/pnas.37.9.570","article-title":"Antibiotic Substances from Basidiomycetes: VIII. 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