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Due to its beneficial effects on metabolic regulation, inflammation suppression, cell death prevention, and fibrogenesis inhibition, farnesoid X receptor (FXR) is widely accepted as a promising therapeutic target for nonalcoholic steatosis (NASH) or called metabolic dysfunction\u2010associated steatohepatitis (MASH). Many FXR agonists have been developed for NASH\/MASH therapy. Obeticholic acid (OCA) is the pioneering frontrunner FXR agonist and the first demonstrating success in clinical trials. Unfortunately, OCA did not receive regulatory approval as a NASH pharmacotherapy because its moderate benefits did not outweigh its safety risks, which may cast a shadow over FXR\u2010based drug development for NASH\/MASH. This review summarizes the milestones in the development of OCA for NASH\/MASH and discuss its limitations, including moderate hepatoprotection and the undesirable side effects of dyslipidemia, pruritus, cholelithiasis, and liver toxicity risk, in depth. More importantly, we provide perspectives on FXR\u2010based therapy for NASH\/MASH, hoping to support a successful bench\u2010to\u2010clinic transition.<\/jats:p>","DOI":"10.1002\/med.21991","type":"journal-article","created":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T03:33:35Z","timestamp":1698636815000},"page":"568-586","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":123,"title":["FXR agonists for MASH therapy: Lessons and perspectives from obeticholic acid"],"prefix":"10.1002","volume":"44","author":[{"given":"Kang","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuecan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University Nanjing 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