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While metformin effectively inhibits renal cyst growth in mouse models of ADPKD it exhibits low potency, and thus an adenosine monophosphate\u2010activated protein kinase (AMPK) activator with higher potency is required. Herein, we adopted a drug repurposing strategy to explore the potential of PF\u201006409577, an AMPK activator for diabetic nephropathy, in cellular, <jats:italic>ex\u2009vivo<\/jats:italic> and <jats:italic>in\u2009vivo<\/jats:italic> models of ADPKD. Our results demonstrated that PF\u201006409577 effectively down\u2010regulated mammalian target of rapamycin pathway\u2010mediated proliferation of cyst\u2010lining epithelial cells and reduced cystic fibrosis transmembrane conductance regulator\u2010regulated cystic fluid secretion. Overall, our data suggest that PF\u201006409577 holds therapeutic potential for ADPKD treatment.<\/jats:p>","DOI":"10.1002\/2211-5463.13459","type":"journal-article","created":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T07:39:10Z","timestamp":1656056350000},"page":"1761-1770","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp>PF<\/scp>\u201006409577 inhibits renal cyst progression by concurrently inhibiting the <scp>mTOR<\/scp> pathway and <scp>CFTR<\/scp> channel activity"],"prefix":"10.1002","volume":"12","author":[{"given":"Limin","family":"Su","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoxing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical 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