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Med."},{"key":"10.1016\/j.ejmech.2026.119157_bib88","doi-asserted-by":"crossref","first-page":"91258","DOI":"10.18632\/oncotarget.20440","article-title":"A small molecule, (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol suppresses tumor growth via inhibition of IkappaB kinase \u03b2 in colorectal cancer in vivo and in vitro","volume":"8","author":"Zheng","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.ejmech.2026.119157_bib89","doi-asserted-by":"crossref","first-page":"2632","DOI":"10.3390\/ijms20112632","article-title":"(E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol ameliorates MPTP-induced dopaminergic neurodegeneration by inhibiting the STAT3 pathway","volume":"20","author":"Choi","year":"2019","journal-title":"Int. J. Mol. 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