Design of potent and highly selective inhibitors for human β-secretase 2 (memapsin 1), a target for type 2 diabetes

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 se...

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Autores principales: Ghosh, Arun K., Reddy, Bhavanam Sekhara, Yen, Yu-Chen, Cárdenas, Emilio L., Rao, Kalapala Venkateswara, Downs, Deborah, Huang, Xiangping, Tang, Jordan, Mesecar, Andrew D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2016
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916918/
https://www.ncbi.nlm.nih.gov/pubmed/27347366
http://dx.doi.org/10.1039/c5sc03718b
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author Ghosh, Arun K.
Reddy, Bhavanam Sekhara
Yen, Yu-Chen
Cárdenas, Emilio L.
Rao, Kalapala Venkateswara
Downs, Deborah
Huang, Xiangping
Tang, Jordan
Mesecar, Andrew D.
author_facet Ghosh, Arun K.
Reddy, Bhavanam Sekhara
Yen, Yu-Chen
Cárdenas, Emilio L.
Rao, Kalapala Venkateswara
Downs, Deborah
Huang, Xiangping
Tang, Jordan
Mesecar, Andrew D.
author_sort Ghosh, Arun K.
collection PubMed
description 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.
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spelling pubmed-49169182017-05-01 Design of potent and highly selective inhibitors for human β-secretase 2 (memapsin 1), a target for type 2 diabetes Ghosh, Arun K. Reddy, Bhavanam Sekhara Yen, Yu-Chen Cárdenas, Emilio L. Rao, Kalapala Venkateswara Downs, Deborah Huang, Xiangping Tang, Jordan Mesecar, Andrew D. Chem Sci Chemistry 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. Royal Society of Chemistry 2016-05-01 2016-02-04 /pmc/articles/PMC4916918/ /pubmed/27347366 http://dx.doi.org/10.1039/c5sc03718b Text en This journal is © The Royal Society of Chemistry 2016 http://creativecommons.org/licenses/by-nc/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported Licence (CC BY-NC 3.0)
spellingShingle Chemistry
Ghosh, Arun K.
Reddy, Bhavanam Sekhara
Yen, Yu-Chen
Cárdenas, Emilio L.
Rao, Kalapala Venkateswara
Downs, Deborah
Huang, Xiangping
Tang, Jordan
Mesecar, Andrew D.
Design of potent and highly selective inhibitors for human β-secretase 2 (memapsin 1), a target for type 2 diabetes
title Design of potent and highly selective inhibitors for human β-secretase 2 (memapsin 1), a target for type 2 diabetes
title_full Design of potent and highly selective inhibitors for human β-secretase 2 (memapsin 1), a target for type 2 diabetes
title_fullStr Design of potent and highly selective inhibitors for human β-secretase 2 (memapsin 1), a target for type 2 diabetes
title_full_unstemmed Design of potent and highly selective inhibitors for human β-secretase 2 (memapsin 1), a target for type 2 diabetes
title_short Design of potent and highly selective inhibitors for human β-secretase 2 (memapsin 1), a target for type 2 diabetes
title_sort design of potent and highly selective inhibitors for human β-secretase 2 (memapsin 1), a target for type 2 diabetes
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916918/
https://www.ncbi.nlm.nih.gov/pubmed/27347366
http://dx.doi.org/10.1039/c5sc03718b
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