δ-Secretase Inhibitor 11

δ-Secretase inhibitor 11 is an inhibitor of δ-secretase (IC₅₀ = 0.7 µM), also known as asparagine endopeptidase (AEP) and legumain.¹ It is selective for δ-secretase over cathepsin S, cathepsin L, caspase-3, and caspase-8 (IC₅₀s = >200, >200, 31.86, and 86.71 µM, respectively). δ-Secretase inhibitor 11 inhibits δ-secretase in Pala B-lymphoblastoid cells (IC₅₀ = 0.8 µM). It inhibits glucose-oxygen deprivation-induced cell death in primary mouse neurons when used at a concentration of 2 µM. In vivo, δ-secretase inhibitor 11 (10 mg/kg per day) inhibits brain δ-secretase in wild-type mice and transgenic mice expressing human tau^P301S. It reduces the number of cortical and hippocampal tau N368-positive neurons, restores synaptic dysfunction, and improves spatial learning and memory in transgenic mice expressing human tau^P301S. δ-Secretase inhibitor 11 (10 mg/kg) reduces hippocampal amyloid-β (Aβ) deposition and attenuates cognitive deficits in the 5XFAD transgenic mouse model of Alzheimer’s disease.

WARNING This product is not for human or veterinary use.

1. Zhang, Z., Obianyo, O., Dall, E., et al. Inhibition of delta-secretase improves cognitive functions in mouse models of Alzheimer’s disease. Nat. Commun. 8, 14740 (2017).