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Updated: Jul 19, 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
Macrocyclic inhibitors of beta-secretase: functional activity in an animal model
Shawn J Stachel1, Craig A Coburn, Sethu Sankaranarayanan
1Department of Medicinal Chemistry, Biological Chemistry, Molecular Systems and Structural Biology Merck Research Laboratories, Post Office Box 4, West Point, Pennsylvania 19486, USA. shawn_stachel@merck.com
Abstract:
A macrocyclic inhibitor of beta-secretase was designed by covalently cross-linking the P1 and P3 side chains of an isophthalamide-based inhibitor. Macrocyclization resulted in significantly improved potency and physical properties when compared to the initial lead structures. More importantly, these macrocyclic inhibitors also displayed in vivo amyloid lowering when dosed in a murine model.
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