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• W3201174550 abstract "Overactivation of TGF-β/ALK5/Smad signaling pathway has been observed in the advanced stage of various human malignancies. As a key component of TGF-β/ALK5/Smad signaling pathway transduction, TGF-β type I receptor (also known as ALK5) has emerged as a promising therapeutic target for cancer treatment. In this study, to discover a novel ALK5 inhibitor, a commercial natural products library was screened using docking-based virtual screening, followed by luciferase reporter assay. A flavonoid glycoside kaempferol 3-O-gentiobioside (KPF 3-O-G) was identified as a potent ALK5 inhibitor through directly bound to the ATP-site of ALK5, resulting in the inhibitory effects on phosphorylation and translocation of Smad2 and expression of Smad4. Additionally, we found that KPF 3-O-G reduced cell proliferation and inhibited TGF-β-induced cell migration and invasion. Moreover, western blotting and immunofluorescent analysis showed that KPF 3-O-G significantly reversed the TGF-β-induced EMT biomarkers, including upregulation of E-cadherin and downregulation of N-cadherin, vimentin, and snail. In vivo study showed that KPF 3-O-G administration reduced tumor growth in human ovarian cancer xenograft mouse model, without obvious toxic effect. This study provided novel insight into the anticancer effects of KPF-3-O-G and indicated that KPF-3-O-G might be developed as potential therapeutics for cancer treatment after further validation." @default.
• W3201174550 created "2021-09-27" @default.
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• W3201174550 date "2021-09-12" @default.
• W3201174550 modified "2023-10-10" @default.
• W3201174550 title "Kaempferol <scp>3‐O</scp> ‐gentiobioside, an <scp>ALK5</scp> inhibitor, affects the proliferation, migration, and invasion of tumor cells via blockade of the <scp>TGF</scp> ‐β/ <scp>ALK5</scp> /Smad signaling pathway" @default.
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• W3201174550 doi "https://doi.org/10.1002/ptr.7278" @default.
• W3201174550 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34514657" @default.
• W3201174550 hasPublicationYear "2021" @default.
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