Discovery of Orally Available and Brain Penetrant AEP Inhibitors.
Authors:Krummenacher D,He W,Kuhn B,Schnider C,Beurier A,Brom V,Sivasothy T,Marty C,Tosstorff A,Hewings DS,Mesch S,Pinard E,Brändlin M,Hochstrasser R,Westwood P,Rothe J,Kronenberger A,Morandi F,Gutbier S,Schuler A,Heer D,Gloria LE,Joedicke L,Rudolph MG,Müller L,Grüninger F,Baumann K,Kaniyappan S,Manevski N,Bartels B
Journal:Journal of medicinal chemistry
PubMed ID:38090813
Alzheimer's Disease (AD) is the most widespread form of dementia, with one of the pathological hallmarks being the formation of neurofibrillary tangles (NFTs). These tangles consist of phosphorylated Tau fragments. Asparagine endopeptidase (AEP) is a key Tau cleaving enzyme that generates aggregation-prone Tau fragments. Inhibition of AEP to reduce the ... More