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Design of Potent and Highly Selective Inhibitors for Human β-Secretase 2 (Memapsin 1), a Target for Type 2 Diabetes.

ABSTRACT: 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.

SUBMITTER: Ghosh AK

PROVIDER: S-EPMC4916918 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Design of Potent and Highly Selective Inhibitors for Human β-Secretase 2 (Memapsin 1), a Target for Type 2 Diabetes.

Ghosh Arun K AK Reddy Bhavanam Sekhara BS Yen Yu-Chen YC Cardenas Emilio E Rao Kalapala Venketeswara KV Downs Deborah D Huang Xiangping X Tang Jordan J Mesecar Andrew D AD

Chemical science 20160204

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. ...[more]

PMID: 27347366

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