7-MORPHOLIN-4-YL-BENZO[1,2,5]OXADIAZOL-4-YLAMINE

Biological Activity

Compound 11 (CP11) is an orally active and brain-penetrant delta-secretase (δ-secretase; AEP) inhibitor th at selectively blocks AEP (IC50 = 710 nM) but not other related cysteine proteases (Caspase-3/-8 IC50 = 31.86/86.71 μM, Cathepsin-S/-L IC50 >200 μM) via a dual active site-directed and allosteric mode of inhibition. CP11 inhibits Pala cellular AEP activity in cultures (IC50 = 800 nM) and improves cognitive functions in murine models of Alzheimerμs disease (AD) in vivo (10 mg/kg tau P301S or 5xFAD mice via daily p.o.) by reducing tau and APP cleavage, ameliorating synapse loss and augmenting long-term potentiation.