{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T19:48:21Z","timestamp":1778183301603,"version":"3.51.4"},"reference-count":32,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T00:00:00Z","timestamp":1649980800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHS272201100030C"],"award-info":[{"award-number":["HHS272201100030C"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Toxicol"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:p>The iminosugar UV-4 is a broad-spectrum antiviral drug candidate with activity in vitro and in vivo against multiple, diverse viruses. The toxicological profile of UV-4, dosed as the hydrochloride salt, was evaluated in single-dose and repeat-dose oral toxicity studies in mice, rats, dogs, and non-human primates (NHP). No moribundity or deaths were associated with the drug up to the maximum tolerated dose. No treatment-related adverse effects were observed following single oral doses in dogs, rats, and mice up to 250, 400, 1000\u00a0mg\/kg, respectively, and in NHP up to 180\u00a0mg\/kg administered three times daily for 10\u00a0days. UV-4-related findings were generally seen at higher doses after 7- or 14-day exposure. The most common clinical pathology findings (increase in aspartate aminotransferase and decreased platelet count) were consistently found across species and each appeared dose related. The kidney, mesenteric lymph nodes, stomach including gastrointestinal tract, and thymus were identified as target organs in mice, rats, and dogs. In 14-day repeat-dose toxicology studies in mice and dogs conducted in compliance with Good Laboratory Practice regulations, the dog was considered to be the most sensitive species to UV-4 exposure based on the treatment-related adverse effects noted in the identified target organs. The results of these studies demonstrate the safety profile of UV-4 hydrochloride and supported the selection of starting and maximal doses for a single ascending dose first-in-human clinical study.<\/jats:p>","DOI":"10.1177\/10915818221077225","type":"journal-article","created":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T10:29:20Z","timestamp":1650018560000},"page":"182-200","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Investigational New Drug Enabling Nonclinical Safety Assessment of the Iminosugar UV-4, a Broad-Spectrum Host-Targeted Antiviral Agent"],"prefix":"10.1177","volume":"41","author":[{"given":"Jeffry","family":"Shearer","sequence":"first","affiliation":[{"name":"Emergent BioSolutions Inc, Gaithersburg, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Gary Wolfe Toxicology, LLC, Herndon, VA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aruna","family":"Sampath","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions Inc, Gaithersburg, MD, USA"},{"name":"Dynavax Technologies Corporation, Emeryville, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1866-5388","authenticated-orcid":false,"given":"Kelly L.","family":"Warfield","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions Inc, Gaithersburg, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions Inc, Gaithersburg, MD, USA"},{"name":"OncoC4, Rockville, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urban","family":"Ramstedt","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions Inc, Gaithersburg, MD, USA"},{"name":"AbViro, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7497-8253","authenticated-orcid":false,"given":"Anthony","family":"Treston","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions Inc, Gaithersburg, MD, USA"},{"name":"Treadwell Therapeutics, Toronto, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,4,15]]},"reference":[{"key":"bibr1-10915818221077225","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.73.011303.073752"},{"key":"bibr2-10915818221077225","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(87)90168-1"},{"key":"bibr3-10915818221077225","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00028-15"},{"key":"bibr4-10915818221077225","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43030-y"},{"key":"bibr5-10915818221077225","doi-asserted-by":"publisher","DOI":"10.1042\/BST20160182"},{"key":"bibr6-10915818221077225","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01282-0"},{"key":"bibr7-10915818221077225","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2020.104881"},{"key":"bibr8-10915818221077225","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2013.01.004"},{"key":"bibr9-10915818221077225","doi-asserted-by":"publisher","DOI":"10.3390\/v8030071"},{"key":"bibr10-10915818221077225","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0121662"},{"key":"bibr11-10915818221077225","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00168-19"},{"key":"bibr12-10915818221077225","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70730-3"},{"key":"bibr13-10915818221077225","volume-title":"Guide for the Care and Use of Laboratory Animals","author":"National Research Council","year":"2011","edition":"8"},{"key":"bibr14-10915818221077225","doi-asserted-by":"publisher","DOI":"10.1177\/10915818211072842"},{"key":"bibr15-10915818221077225","unstructured":"OECD Chronic Toxicity Studies: OECD Guidelines for Testing of Chemicals Sections 452. 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