δ-Secretase inhibitor 11 (compound 11) is an orally active, potent, BBB-penetrated, non-toxic, selective and specific δ-secretase inhibitor, with an IC50 of 0.7 μM. δ-Secretase inhibitor 11 interacts with both the active site and allosteric site of δ-secretase. δ-Secretase inhibitor 11 attenuates tau and APP (amyloid precursor protein) cleavage. δ-Secretase inhibitor 11 ameliorates synaptic dysfunction and cognitive impairments in tau P301S and 5XFAD transgenic mouse models. δ-Secretase inhibitor 11 can be used for Alzheimer’s disease research.IC50 & Target: IC50: 0.70 ± 0.18 μM (δ-secretase), 31.86 ± 1.94 μM (caspase-3), 86.71 ± 10.31 (caspase-8), >200 μM (cathepsin-S), >200 μM (cathepsin-L)In Vitro: δ-Secretase inhibitor 11 (compound 11) (0-1 μM, 10 min) inhibits δ-secretase in a concentration- and time-dependent manner.
δ-Secretase inhibitor 11 (0-1 μM) selectively blocks tau and APP (amyloid precursor protein) fragmentation by δ-secretase.In Vivo: δ-Secretase inhibitor 11 (compound 11) (10 mg/kg, Orally, once daily for 3 months) attenuates neuronal injury induced by OGD (oxygen-glucose deprivation), and specifically exerts neuroprotective actions.
δ-Secretase inhibitor 11 (0-10 mg/kg, Orally, once daily for 1.5 and 3 months) inhibits δ-secretase activity, attenuates Aβ deposition and cognitive deficits in 5XFAD mouse model.