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Updated: May 31, 2026

Quantitative Measurement of γ-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms
Published on: January 25, 2018
NSAID-derived γ-secretase modulation requires an acidic moiety on the carbazole scaffold
Andrea Zall1, Daniel Kieser, Nicole Höttecke
1Clemens Schöpf-Institute of Chemistry and Biochemistry, Technische Universität Darmstadt, Petersenstr. 22, Darmstadt D-64287, Germany.
Abstract:
Modulation of γ-secretase activity holds potential for the treatment of Alzheimer's disease. Most NSAID-derived γ-secretase modulators feature a carboxylic acid, which may impair blood-brain barrier permeation. The structure activity relationship of 33 carbazoles featuring diverse carboxylic acid isosteres or metabolic precursors thereof was established in a cellular amyloid secretion assay. The modulatory activity was observed for acidic moieties and metabolically labile esters only, which supports our hypothesis of an acid-lysine interaction to be relevant for this type of γ-secretase modulators.
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