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].

Reference:
[1].  Lee SH, Shen GN, Jung YS, et al. Antitumor effect of novel small chemical inhibitors of Snail-p53 binding in K-Ras-mutated cancer cells. Oncogene. 2010 Aug 12;29(32):4576-87.