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Overview
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Background
GN25 is a novel inhibitor of Snail-p53 binding [1]. P53 is a tumor suppressor that induces cell death, growth arrest and suppresses metastasis, and is often mutated or suppressed by various kinds of cellular signaling pathways in human cancers. In K-Ras-activated cancer cells, oncogenic K-Ras inhibits the p53 function through induction of Snail, which binds to and eliminates p53 through exocytosis. The specific inhibitor against p53-Snail binding would be used as anticancer drug against K-Ras-mutated or Snail-overexpressed cancers such as colon, pancreatic and lung cancers [1]. GN25 is a novel and specific inhibitor of Snail-p53 binding. GN25 is a 2-thio-dimethoxy naphthoquinone analog that induces p53 and p21 expression, and blocks the p53-Snail binding. In K-Ras-transformed mouse embryonic fibroblast (MEF), GN25 induced p53 and p21 in K-Ras-dependent way. In assay with capan-1 extract, GN25 significantly reduced interaction between p53 and Snail [1]. In nude mice inoculated A549 cells through i.p. injection, GN25 blocked the tumor progression and also induced tumor regression [1].
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