Merck, 565789-1MGCN, γ-Secretase Inhibitor XX

A cell-permeable dibenzazepine (dbz) compound that acts as a potent γ-secretase inhibitor and significantly lowers both brain and plasma Aβ₄₀ levels by ~72% in Tg2576 mutant APP transgenic mouse model (100 µmol/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 µmol/kg, i.p).