Chemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of β-secretase inhibitors

Chemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of β-secretase inhibitors

Several β-secretase (BACE) inhibitors exhibit unexplained ocular toxicity in preclinical studies. Here the authors generate a clickable photoaffinity probe to interrogate off-targets in cells and animals, and identify inhibition of cathepsin D as a driver of ocular toxicity.

Bibliographic Details
Main Authors: Andrea M. Zuhl, Charles E. Nolan, Michael A. Brodney, Sherry Niessen, Kevin Atchison, Christopher Houle, David A. Karanian, Claude Ambroise, Jeffrey W. Brulet, Elizabeth M. Beck, Shawn D. Doran, Brian T. O’Neill, Christopher W. am Ende, Cheng Chang, Kieran F. Geoghegan, Graham M. West, Joshua C. Judkins, Xinjun Hou, David R. Riddell, Douglas S. Johnson
Format: Article
Language:English
Published: Nature Portfolio 2016-10-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/ncomms13042

Internet

https://doi.org/10.1038/ncomms13042

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