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Cell Res. 2016 Apr;26(4):484-98. doi: 10.1038/cr.2016.31. Epub 2016 Mar 22.

Drugging the undruggables: exploring the ubiquitin system for drug development.

Author information

1
Department of Discovery Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA;
2
Department of Physiological Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Abstract

Dynamic modulation of protein levels is tightly controlled in response to physiological cues. In mammalian cells, much of the protein degradation is carried out by the ubiquitin-proteasome system (UPS). Similar to kinases, components of the ubiquitin system are often dysregulated, leading to a variety of diseases, including cancer and neurodegeneration, making them attractive drug targets. However, so far there are only a handful of drugs targeting the ubiquitin system that have been approved by the FDA. Here, we review possible therapeutic intervention nodes in the ubiquitin system, analyze the challenges, and highlight the most promising strategies to target the UPS.

PMID:
27002218
PMCID:
PMC4822129
DOI:
10.1038/cr.2016.31
[Indexed for MEDLINE]
Free PMC Article

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