begacestat

Begacestat is a small molecule investigational drug developed as a selective thiophene sulfonamide inhibitor of gamma-secretase. Gamma-secretase is an intramembrane protease complex responsible for the cleavage of amyloid precursor protein (APP), leading to the production of amyloid-beta peptides implicated in Alzheimer's disease pathology. Begacestat selectively inhibits gamma-secretase-mediated cleavage of APP over Notch receptor processing (approximately 16-fold selectivity), aiming to reduce neurotoxic amyloid-beta peptide formation while minimizing adverse effects associated with Notch inhibition. Preclinical studies demonstrated robust reductions in brain and plasma amyloid-beta levels and reversal of cognitive deficits in animal models. In clinical trials, begacestat showed dose-dependent pharmacodynamic effects on plasma amyloid-beta levels in humans. Its primary indication was for the treatment of Alzheimer's disease[1][3][4][5][6][8].

Other names

begacestat769169-27-95-chloro-N-[(2S)-4,4,4-trifluoro-1-hydroxy-3-(trifluoromethyl)butan-2-yl]thiophene-2-sulfonamide