{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T03:04:58Z","timestamp":1772507098594,"version":"3.50.1"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"20","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1S10RR022984-01A1"],"award-info":[{"award-number":["1S10RR022984-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1S10OD018091-01"],"award-info":[{"award-number":["1S10OD018091-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Uridine diphosphate glucunosyltransferases (UGTs) metabolize 15% of FDA approved drugs. Lead optimization efforts benefit from knowing how candidate drugs are metabolized by UGTs. This paper describes a computational method for predicting sites of UGT-mediated metabolism on drug-like molecules.<\/jats:p>\n               <jats:p>Results: XenoSite correctly predicts test molecule\u2019s sites of glucoronidation in the Top-1 or Top-2 predictions at a rate of 86 and 97%, respectively. In addition to predicting common sites of UGT conjugation, like hydroxyl groups, it can also accurately predict the glucoronidation of atypical sites, such as carbons. We also describe a simple heuristic model for predicting UGT-mediated sites of metabolism that performs nearly as well (with, respectively, 80 and 91% Top-1 and Top-2 accuracy), and can identify the most challenging molecules to predict on which to assess more complex models. Compared with prior studies, this model is more generally applicable, more accurate and simpler (not requiring expensive quantum modeling).<\/jats:p>\n               <jats:p>Availability and implementation: The UGT metabolism predictor developed in this study is available at http:\/\/swami.wustl.edu\/xenosite\/p\/ugt.<\/jats:p>\n               <jats:p>Contact: swamidass@wustl.edu<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btw350","type":"journal-article","created":{"date-parts":[[2016,6,21]],"date-time":"2016-06-21T01:40:18Z","timestamp":1466473218000},"page":"3183-3189","source":"Crossref","is-referenced-by-count":76,"title":["A simple model predicts UGT-mediated metabolism"],"prefix":"10.1093","volume":"32","author":[{"given":"Na Le","family":"Dang","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, 660\u2009S. Euclid Ave, St. Louis, MO 63110, USA"}]},{"given":"Tyler B.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, 660\u2009S. Euclid Ave, St. Louis, MO 63110, USA"}]},{"given":"Varun","family":"Krishnamurthy","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, 660\u2009S. Euclid Ave, St. Louis, MO 63110, USA"}]},{"given":"S. Joshua","family":"Swamidass","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, 660\u2009S. Euclid Ave, St. Louis, MO 63110, USA"}]}],"member":"286","published-online":{"date-parts":[[2016,6,20]]},"reference":[{"key":"2023020113485507100_btw350-B1","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1002\/elps.200410301","article-title":"Analysis of oxycodol and noroxycodol stereoisomers in biological samples by capillary electrophoresis","volume":"26","author":"Baldacci","year":"2005","journal-title":"Electrophoresis"},{"key":"2023020113485507100_btw350-B2","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1158\/1078-0432.1226.11.3","article-title":"Ugt1a7 and ugt1a9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine\/irinotecan","volume":"11","author":"Carlini","year":"2005","journal-title":"Clinical Cancer Research"},{"key":"2023020113485507100_btw350-B3","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1124\/dmd.107.018234","article-title":"Biotransformation of [14c] dasatinib: in vitro studies in rat, monkey, and human and disposition after administration to rats and monkeys","volume":"36","author":"Christopher","year":"2008","journal-title":"Drug Metab. Dispos"},{"key":"2023020113485507100_btw350-B4","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1124\/jpet.110.170555","article-title":"In vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and metabolism of 10074-g5, a novel small-molecule inhibitor of c-myc\/max dimerization","volume":"335","author":"Clausen","year":"2010","journal-title":"J. Pharmacol. Exp. Therap"},{"key":"2023020113485507100_btw350-B9","doi-asserted-by":"crossref","first-page":"102","DOI":"10.4172\/2157-7609.1000102","article-title":"Metabolites in safety testing: issues and approaches to the safety evaluation of human metabolites in a drug that is extensively metabolized","volume":"1","author":"Griffini","year":"2010","journal-title":"J. Drug Metab. Toxicol"},{"key":"2023020113485507100_btw350-B5","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1124\/dmd.105.004283","article-title":"Metabolism and disposition of imatinib mesylate in healthy volunteers","volume":"33","author":"Gschwind","year":"2005","journal-title":"Drug Metab. Dispos"},{"key":"2023020113485507100_btw350-B6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0169-2607(99)00046-2","article-title":"Application of neural networks and sensitivity analysis to improved prediction of trauma survival","volume":"62","author":"Hunter","year":"2000","journal-title":"Comput. Methods Prog. Biomed"},{"key":"2023020113485507100_btw350-B7","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/med.1016","article-title":"Role of drug metabolism in drug discovery and development","volume":"21","author":"Kumar","year":"2001","journal-title":"Med. Res. Rev"},{"key":"2023020113485507100_btw350-B8","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1758-2946-3-33","article-title":"Open babel: an open chemical toolbox","volume":"3","author":"OLBoyle","year":"2011","journal-title":"J. Cheminf"},{"key":"2023020113485507100_btw350-B10","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1093\/bioinformatics\/btt681","article-title":"In silico site of metabolism prediction for human ugt-catalyzed reactions","volume":"30","author":"Peng","year":"2014","journal-title":"Bioinformatics"},{"key":"2023020113485507100_btw350-B11","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1124\/dmd.30.5.505","article-title":"Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization","volume":"30","author":"Prueksaritanont","year":"2002","journal-title":"Drug Metab. Dispos"},{"key":"2023020113485507100_btw350-B12","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/clpt.2009.181","article-title":"Udp-glucuronosyltransferase (ugt) polymorphisms affect atorvastatin lactonization in vitro and in vivo","volume":"87","author":"Riedmaier","year":"2010","journal-title":"Clin. Pharmacol. Ther"},{"key":"2023020113485507100_btw350-B13","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1124\/dmd.31.6.731","article-title":"The disposition of voriconazole in mouse, rat, rabbit, guinea pig, dog, and human","volume":"31","author":"Roffey","year":"2003","journal-title":"Drug Metab. Dispos"},{"key":"2023020113485507100_btw350-B14","first-page":"btv087","article-title":"Somp: web-server for in silico prediction of sites of metabolism for drug-like compounds","volume":"10","author":"Rudik","year":"2015","journal-title":"Bioinformatics"},{"key":"2023020113485507100_btw350-B15","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1021\/ml100016x","article-title":"Smartcyp: a 2d method for prediction of cytochrome p450-mediated drug metabolism","volume":"1","author":"Rydberg","year":"2010","journal-title":"ACS Med. Chem. Lett"},{"key":"2023020113485507100_btw350-B16","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1021\/jm020400s","article-title":"A model for predicting likely sites of cyp3a4-mediated metabolism on drug-like molecules","volume":"46","author":"Singh","year":"2003","journal-title":"J. Med. Chem"},{"key":"2023020113485507100_btw350-B17","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1093\/bioinformatics\/btq140","article-title":"A croc stronger than roc: measuring, visualizing and optimizing early retrieval","volume":"26","author":"Swamidass","year":"2010","journal-title":"Bioinformatics"},{"key":"2023020113485507100_btw350-B18","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1124\/dmd.104.003491","article-title":"Differential rates of glucuronidation for 7-ethyl-10-hydroxy-camptothecin (sn-38) lactone and carboxylate in human and rat microsomes and recombinant udp-glucuronosyltransferase isoforms","volume":"33","author":"Tallman","year":"2005","journal-title":"Drug Metab. Dispos"},{"key":"2023020113485507100_btw350-B19","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1124\/dmd.110.032250","article-title":"Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects","volume":"38","author":"Teng","year":"2010","journal-title":"Drug Metab. Dispos"},{"key":"2023020113485507100_btw350-B20","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1211\/0022357991776697","article-title":"High-performance liquid-chromatographic-atmospheric-pressure chemical-ionization ion-trap mass-spectrometric identification of isomeric c6-hydroxy and c20-hydroxy metabolites of methylprednisolone in the urine of patients receiving high-dose pulse therapy","volume":"51","author":"VREE","year":"1999","journal-title":"J. Pharm. Pharmacol"},{"key":"2023020113485507100_btw350-B21","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1124\/dmd.104.000794","article-title":"Drug-drug interactions for udp-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (auci\/auc) ratios","volume":"32","author":"Williams","year":"2004","journal-title":"Drug Metab. Dispos"},{"key":"2023020113485507100_btw350-B22","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1021\/ci400518g","article-title":"Xenosite: accurately predicting cyp-mediated sites of metabolism with neural networks","volume":"53","author":"Zaretzki","year":"2013","journal-title":"J. Chem. Inform. Model"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/20\/3183\/49022330\/bioinformatics_32_20_3183.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/20\/3183\/49022330\/bioinformatics_32_20_3183.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T23:52:39Z","timestamp":1675295559000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/32\/20\/3183\/2196454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,20]]},"references-count":22,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2016,10,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btw350","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2016,10,15]]},"published":{"date-parts":[[2016,6,20]]}}}