ArticleArchives of pharmacal research2026
Discovery of a potent STAT3 inhibitor WR-S-647 for the treatment of ADPKD.
Article in Archives of pharmacal research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors.
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Abstract
Autosomal dominant polycystic kidney disease (ADPKD) affects approximately 12.5 million individuals globally and is one of the most common causes of end-stage renal disease. It is typically associated with a gradual increase in the volume of numerous cysts in both kidneys. Recent studies have highlighted the critical role of signal transducer and activator of transcription 3 (STAT3) in ADPKD pathogenesis, as it is highly expressed and persistently activated in ADPKD kidneys. Through screening of our in-house compound library, we identified compound WR-S-647 (4e) as a potent and specific inhibitor of STAT3 with a binding affinity of 34 nM to STAT3. WR-S-647 suppressed the phosphorylation activation and nuclear localization of STAT3. In vitro, WR-S-647 remarkably suppressed cyst formation and expansion in a Madin-Darby canine kidney (MDCK) cyst model. Meanwhile, it effectively diminished cyst growth in an ex vivo embryonal renal cyst model and an in vivo Pkd1 knockout ADPKD mouse model. Our study identifies WR-S-647 as a potent STAT3-mediated inhibitor and provides preclinical proof-of-concept for its efficacy in reducing cyst growth in ADPKD models.
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