A cell-permeable compound that targets β-catenin via direct affinity interaction within the C-terminal two thirds (a.a. 301-670) of the Armadillo repeat region (a.a. 136–686), inducing β-catenin ubiquitination and proteasomal degradation (Eff. conc. 1.25-5 μM in DLD-1, SW480 and LS174T cultures). MSAB selectively inhibits against Wnt sginaling-dependent proliferation of cancer cells (IC50 <6 μM), while exhibiting little efficacy in Wnt-independent cultures (<10% inhibition at 10 μM). Likewise, daily intraperitoneal injection (10-20 mg/kg/day) is efficacious in suppressing the expansion of established tumors from HCT116, HT115, and H23 xenografts in mice, while exhibiting little efficacy against the Wnt-independent H460 tumor growth.
A cellular β-catenin degradation inducer with anti-proliferation efficacy against Wnt-dependent cancer growth both in vitro and in vivo.
