Design of potent and highly selective inhibitors for human β-secretase 2 (memapsin 1), a target for type 2 diabetes
Arun Kumar Ghosh, Bhavanam Sekhara Reddy, Yu‐Chen Yen, Emilio L. Cárdenas, Kalapala Venkateswara Rao, Deborah Downs, Xiangping Huang, Jordan Tang, Andrew D. Mesecar · Chemical Science · 2016
Design, synthesis and evaluation of very potent and selective β-Secretase 2 (memapsin 1, BACE 2) inhibitors are described. The inhibitors were designed specifically to interact with the S2'-site of β-secretase 2 to provide >170,000-fold selectivity over β-secretase (BACE 1) and >15,000-fold selectivity over cathepsin D. BACE 2 is implicated in Type 2 diabetes. The studies serve as an important guide to selective BACE 2 inhibitors.