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...

Descripción completa

Detalles Bibliográficos
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
Descripción
Sumario: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.

Ejemplares similares