BMS299897

Description	BMS 299897 is a selective inhibitor for gamma-secretase. Reductions in the formation of Abeta peptides by gamma-secretase inhibitors may be a viable therapy for reducing Abeta in Alzheimer's disease. BMS-299897 is a gamma-secretase inhibitor that was effective in reducing amyloid beta-peptide (A beta) in transgenic mice and guinea pigs. in vitro: BMS-299897 dose-dependently increased brain concentrations of APP carboxy-terminal fragments, consistent with inhibition of gamma-secretase. BMS-299897 (100 mg/kg po) reduced brain and plasma Abeta(1-40) rapidly (within 20min) and maximally within 3 h. BMS-299897 dose-dependently reduced cortical, cerebrospinal fluid (CSF), and plasma Abeta in guinea pigs with ED(50) values of 30 mg/kg intraperitoneally, without affecting CSF levels of alpha-sAPP. The reductions in cortical Abeta correlated significantly with the reductions in both plasma (r(2) = 0.77) and CSF (r(2) = 0.61) Abeta . in vivo: BMS-299897blocked the Aβ(25-35)-induced deficits in s
Pathways	Protease/Metabolic Enzyme Neuro Signaling Pathway Wnt/Stem Cell
Targets	Gamma secretase

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