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Description

A cell-permeable, potent gamma-secretase inhibitor that significantly lowers both brain and plasma Abeta40 levels by ~72% in Tg2576 mutant APP transgenic mouse model (100 µ,mol/kg, b.i.d). Induces a heterogeneous reorganization of the crypt structural-proliferative units in the intestinal tract and of the stem cell niche in the colon. Also potently inhibits Notch processing (IC50 = 1.7 nM in SupT1 cells) and induces conversion of proliferative crypt cells to post-mitotic goblet cells in both the C57BL/6 and ApcMin mouse models (10 µ,mol/kg, i.p)., A cell-permeable dibenzazepine (dbz) compound that acts as a potent gamma-secretase inhibitor and significantly lowers both brain and plasma Abeta40 levels by ~72% in Tg2576 mutant APP transgenic mouse model (100 µ,mol/kg, b.i.d). Induces a heterogeneous reorganization of the crypt structural-proliferative units in the intestinal tract and of the stem cell niche in the colon. Also potently inhibits Notch processing (IC50 = 1.7 nM in SupT1 cells) and induces conversion of proliferative crypt cells to post-mitotic goblet cells in both the C57BL/6 and ApcMin mouse models (10 µ,mol/kg, i.p).