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Despite its success, patients suffer dose\u2010dependent diarrhea, limiting the drug's efficacy. No effective therapy is available for this unmet medical need. The bacterial \u03b2\u2010glucuronidase (\u03b2\u2010GUS) plays pivotal role in CPT\u201011\u2010induced diarrhea (CID) via activating the non\u2010toxic SN\u201038G to toxic SN\u201038 inside intestine. By using structural\u2010based virtual screening, three old drugs (<jats:italic>N<\/jats:italic>\u2010Desmethylclozapine, Aspartame, and Gemifloxacin) were firstly identified as selective bacterial \u03b2\u2010GUS inhibitors. The IC<jats:sub>50<\/jats:sub> values of the compounds in the enzyme\u2010based and cell\u2010based assays range from 0.0389 to 3.6040 and 0.0105 to 5.3730\u00a0\u03bcM, respectively. The compounds also showed good selectivity against mammalian \u03b2\u2010GUS and no significant cytotoxicity in bacteria. Molecular docking and molecular dynamics simulations were performed to further investigate the binding modes of compounds with bacterial \u03b2\u2010GUS. Binding free energy decomposition revealed that the compounds formed strong interactions with E413 in catalytic trail from primary monomer and F365\u2032 on the bacterial loop from the other monomer of bacterial \u03b2\u2010GUS, explaining the selectivity against mammalian \u03b2\u2010GUS. The old drugs identified here may be used as bacterial \u03b2\u2010GUS inhibitors for CID or other bacterial \u03b2\u2010GUS\u2010related disorders.<\/jats:p>","DOI":"10.1111\/cbdd.13655","type":"journal-article","created":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T18:14:06Z","timestamp":1576260846000},"page":"368-379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Identify old drugs as selective bacterial \u03b2\u2010GUS inhibitors by structural\u2010based virtual screening and bio\u2010evaluations"],"prefix":"10.1111","volume":"95","author":[{"given":"Zhou","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Bioinformatics and Medical Engineering School of Electrical and Information Engineering School of Chemical and Environmental Engineering Jiangsu University of Technology Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshuang","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Medical Engineering School of Electrical and Information Engineering School of Chemical and Environmental Engineering Jiangsu University of Technology Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianhua","family":"Piao","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Medical Engineering School of Electrical and Information Engineering School of Chemical and Environmental Engineering Jiangsu University of Technology Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Medical Engineering School of Electrical and Information Engineering School of Chemical and Environmental Engineering Jiangsu University of Technology Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Fudan University Shanghai Cancer Center Shanghai China"},{"name":"Department of Oncology Shanghai Medical College Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9010-1750","authenticated-orcid":false,"given":"Ren","family":"Kong","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Medical Engineering School of Electrical and Information Engineering School of Chemical and Environmental Engineering Jiangsu University of Technology Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/86.6.446"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057112444927"},{"key":"e_1_2_10_4_1","first-page":"27","article-title":"CPT\u201011: Clinical experience in phase I studies","volume":"23","author":"Armand J. 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