γ-Secretase is a multi-subunit aspartyl protease that cleaves amyloid precursor protein (APP) and many other type 1 transmembrane proteins, including Notch, E-cadherin, and ErbB4. The proteolysis of APP by secretases produces beta amyloid (Aβ), a 39- to 42-amino acid peptide which forms the amyloid plaques that are characteristic of Alzheimer’s disease. DBZ is a dipeptidic inhibitor of γ-secretase that potently blocks the cleavage of Notch into its active signaling effector, Notch intracellular domain, in human T cell lymphoma (SupT1) cells (IC50 = 1.7 nM). Within 4 hours after a single 100 μM/kg dose, DBZ demonstrates anti-Alzheimer activity in an APP transgenic mouse model characterized by high levels of Aβ40 by reducing Aβ40 levels by 71%.
γ-Secretase is a multi-subunit aspartyl protease that cleaves amyloid precursor protein (APP) and many other type 1 transmembrane proteins, including Notch, E-cadherin, and ErbB4. The proteolysis of APP by secretases produces beta amyloid (Aβ), a 39- to 42-amino acid peptide which forms the amyloid plaques that are characteristic of Alzheimer’s disease. DBZ is a dipeptidic inhibitor of γ-secretase that potently blocks the cleavage of Notch into its active signaling effector, Notch intracellular domain, in human T cell lymphoma (SupT1) cells (IC50 = 1.7 nM). Within 4 hours after a single 100 μM/kg dose, DBZ demonstrates anti-Alzheimer activity in an APP transgenic mouse model characterized by high levels of Aβ40 by reducing Aβ40 levels by 71%.
DIBENZAZEPINE is a dipeptidic-secretase inhibitor and a antiAlzheimer agent.
A dipeptidic γ-secretase inhibitor. AntiAlzheimer agent.
A cell-permeable, potent γ-secretase inhibitor that 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).
