biostudies-literatureSu LNational Natural Science Foundation of ChinaNatural Science Research of Jiangsu Higher Education Institutions of ChinaNatural Science Foundation of Jiangsu Province1761-1770https://www.ebi.ac.uk/biostudies/studies/S-EPMC9527591biostudies-literatureUnknown12(10)Renal cyst development and expansion in autosomal dominant polycystic kidney disease (ADPKD) involves over-proliferation of cyst-lining epithelial cells and excessive cystic fluid secretion. While metformin effectively inhibits renal cyst growth in mouse models of ADPKD it exhibits low potency, and thus an adenosine monophosphate-activated protein kinase (AMPK) activator with higher potency is required. Herein, we adopted a drug repurposing strategy to explore the potential of PF-06409577, an AMPK activator for diabetic nephropathy, in cellular, ex vivo and in vivo models of ADPKD. Our results demonstrated that PF-06409577 effectively down-regulated mammalian target of rapamycin pathway-mediated proliferation of cyst-lining epithelial cells and reduced cystic fibrosis transmembrane conductFEBS open bioPF-06409577 inhibits renal cyst progression by concurrently inhibiting the mTOR pathway and CFTR channel activity.PMC9527591BK202001068180360920KJA35000122077110Liu HWang RZhang HRen YFang QSu LGuo DFu KYuan HYin LWang JfalsePF-06409577 inhibits renal cyst progression by concurrently inhibiting the mTOR pathway and CFTR channel activity.Renal cyst development and expansion in autosomal dominant polycystic kidney disease (ADPKD) involves over-proliferation of cyst-lining epithelial cells and excessive cystic fluid secretion. While metformin effectively inhibits renal cyst growth in mouse models of ADPKD it exhibits low potency, and thus an adenosine monophosphate-activated protein kinase (AMPK) activator with higher potency is required. Herein, we adopted a drug repurposing strategy to explore the potential of PF-06409577, an AMPK activator for diabetic nephropathy, in cellular, ex vivo and in vivo models of ADPKD. Our results demonstrated that PF-06409577 effectively down-regulated mammalian target of rapamycin pathway-mediated proliferation of cyst-lining epithelial cells and reduced cystic fibrosis transmembrane conduct2022-01-01T00:00:00Z2022 Oct2025-04-05T07:08:39.753Z2024-11-12T02:44:24.294ZS-EPMC95275913574809710.1002/2211-5463.13459