{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:20:20Z","timestamp":1789993220706,"version":"4.0.1"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,2,21]],"date-time":"2014-02-21T00:00:00Z","timestamp":1392940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>High\u2010content imaging\/analysis has emerged as a powerful tool for predictive toxicology as it can be used for identifying and mitigating potential safety risks during drug discovery. By careful selection of end\u2010points, some cellular assays can show better predictivity than routine animal toxicity testing for certain adverse events. Here, we present the perhaps most utilized high\u2010content screening assays for predictive toxicology in the pharmaceutical industry. Multi\u2010parametric imaging of cell health in simple and cost\u2010effective model systems can be used to predict human hepatotoxicity and elucidate mechanisms of toxicity, and imaging of bile salt transport inhibition in sandwich\u2010cultured hepatocytes can be used to predict cholestasis\u2010inducing compounds. Imaging of micronuclei formation in simple cell models can be used to detect genotoxic potential and elucidate anuegenic or clastogenic mode of actions. The hope is that application of these relatively predictive assays during drug discovery will reduce toxicity and safety\u2010related attrition of drug development programmes at later stages.<\/jats:p>","DOI":"10.1111\/bcpt.12200","type":"journal-article","created":{"date-parts":[[2014,1,25]],"date-time":"2014-01-25T09:05:28Z","timestamp":1390640728000},"page":"18-23","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["High\u2010Content Analysis\/Screening for Predictive Toxicology: Application to Hepatotoxicity and Genotoxicity"],"prefix":"10.1111","volume":"115","author":[{"given":"Mikael","family":"Persson","sequence":"first","affiliation":[{"name":"Department of Exploratory Toxicology Non\u2010Clinical Safety Research H. Lundbeck A\/S Valby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anni F.","family":"L\u00f8ye","sequence":"additional","affiliation":[{"name":"Department of Exploratory Toxicology Non\u2010Clinical Safety Research H. Lundbeck A\/S Valby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Jacquet","sequence":"additional","affiliation":[{"name":"Department of Exploratory Toxicology Non\u2010Clinical Safety Research H. Lundbeck A\/S Valby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natacha S.","family":"Mow","sequence":"additional","affiliation":[{"name":"Department of Exploratory Toxicology Non\u2010Clinical Safety Research H. Lundbeck A\/S Valby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemette V.","family":"Thougaard","sequence":"additional","affiliation":[{"name":"Department of Exploratory Toxicology Non\u2010Clinical Safety Research H. Lundbeck A\/S Valby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Mow","sequence":"additional","affiliation":[{"name":"Department of Exploratory Toxicology Non\u2010Clinical Safety Research H. Lundbeck A\/S Valby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorrit J.","family":"Hornberg","sequence":"additional","affiliation":[{"name":"Department of Exploratory Toxicology Non\u2010Clinical Safety Research H. Lundbeck A\/S Valby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,21]]},"reference":[{"key":"e_1_2_6_2_1","article-title":"Exploratory toxicology as an integrated part of drug discovery \u2010 Part I: why and how","author":"Hornberg JJ","year":"2013","journal-title":"Drug Discov Today"},{"key":"e_1_2_6_3_1","article-title":"Exploratory toxicology as an integrated part of drug discovery \u2010 Part II: screening strategies","author":"Hornberg JJ","year":"2013","journal-title":"Drug Discov Today"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-006-0091-3"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfn109"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2013.08.001"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfs083"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2007.07.013"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/KFS197"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfl180"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx200168d"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.027797"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.3019"},{"key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1242\/jeb.204.10.1673","article-title":"Transport of bile acids in hepatic and non\u2010hepatic tissues","volume":"204","author":"St\u2010Pierre MV","year":"2001","journal-title":"J Exp Biol"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2012.06.006"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.040758"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602530903492004"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kft197"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2010.03.008"},{"key":"e_1_2_6_20_1","first-page":"447","article-title":"Cholyllysyl fluroscein and related lysyl fluorescein conjugated bile acid analogues","volume":"70","author":"Mills CO","year":"1997","journal-title":"Yale J Biol Med"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfq044"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.29608"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx300091x"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2012.10.011"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-011-0691-4"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.93101s3101"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2007.03.002"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1218(97)00047-5"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112320"},{"key":"e_1_2_6_30_1","article-title":"Guideline on genotoxicity testing and data interpretation for pharmaceuticals intended for human use S2(R1)","author":"ICH Guideline S2 (R1)","year":"2011","journal-title":"EMEA"}],"container-title":["Basic &amp; Clinical Pharmacology &amp; Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcpt.12200","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.12200","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T02:02:55Z","timestamp":1696298575000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcpt.12200"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2,21]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,7]]}},"alternative-id":["10.1111\/bcpt.12200"],"URL":"https:\/\/doi.org\/10.1111\/bcpt.12200","archive":["Portico"],"relation":{},"ISSN":["1742-7835","1742-7843"],"issn-type":[{"value":"1742-7835","type":"print"},{"value":"1742-7843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2,21]]},"assertion":[{"value":"2013-11-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-01-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-02-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}