LY2811376

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Description

LY2811376 is the first orally available non-peptidic BACE1 inhibitor that produces profound Aβ-lowering effects in animals. LY2811376 has 10-fold selectivity towards BACE1 over BACE2, and more than 50-fold inhibition over other aspartic proteases including cathepsin D, pepsin, or renin. LY2811376 inhibits Aβ secretion with EC50 of ~100 nM in primary neuronal cultures of PDAPP transgenic mouse. Administration of LY2811376 (10, 30 and 100 mg/kg doses) results in dose-dependent, significant reductions in Aβ, as well as sAPPβ and C99. LY2811376 treatment yields a concentration-dependent decrease in Aβ secretion in APP-overexpressing HEK293 cells.

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