LY2811376 is a potent and selective BACE1 inhibitor (IC50 = 239 nM for the synthetic peptide) that demonstrates ~10-fold selectivity over BACE2 and >50-fold selectivity over the aspartyl proteases cathepsin D, pepsin, and renin.3 LY2811376 treatment induces Aβ5-X peptides through alternative amyloid precursor protein cleavage. The β-secretase enzyme, β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), cleaves amyloid precursor protein (APP) in the first step in β-amyloid (Aβ) peptide production. Thus, BACE1 is a key target for candidate disease-modifying treatment of Alzheimer's disease.