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Therefore, it is necessary to develop effective therapeutic drugs for APAP\u2010induced hepatotoxicity. Farnesoid X receptor (FXR) is a potential target for the treatment of liver disease, and the activation of FXR protects mice against APAP\u2010induced hepatotoxicity. Compound <jats:bold>5<\/jats:bold>, a glycine\u2010conjugated derivative of FXR agonist <jats:bold>4<\/jats:bold>, was designed to extend the chemical space of existing FXR agonists. Molecular modeling study indicated that compound <jats:bold>5<\/jats:bold> formed hydrogen bond network with key residues of FXR. Moreover, compound <jats:bold>5<\/jats:bold> (10\u00a0mg\/kg) revealed better protective effects against APAP\u2010induced hepatotoxicity than parent compound <jats:bold>4<\/jats:bold> (30\u00a0mg\/kg). Further mechanical research indicated that compound <jats:bold>5<\/jats:bold> regulated the expressions of genes related to FXR and oxidative stress. These findings suggest that compound <jats:bold>5<\/jats:bold> is a promising FXR agonist suitable for further research, and it is the first time to verify that the glycine\u2010conjugated derivative five exerted better protective effects than its parent compound.<\/jats:p>","DOI":"10.1111\/cbdd.14014","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T14:11:40Z","timestamp":1640182300000},"page":"483-495","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Discovery of a novel and orally active Farnesoid X receptor agonist for the protection of acetaminophen\u2010induced hepatotoxicity"],"prefix":"10.1111","volume":"99","author":[{"given":"Zongyu","family":"Cai","sequence":"first","affiliation":[{"name":"School of Pharmacy Guangdong Pharmaceutical University  Guangzhou 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