Volume 26, No 4, Apr 2016

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 26 Issue 4, April 2016: 484-498   |  Open Access

REVIEWS

Drugging the undruggables: exploring the ubiquitin system for drug development

Xiaodong Huang¹ and Vishva M Dixit²

¹Department of Discovery Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA;
²Department of Physiological Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA Correspondence: Xiaodong Huang, E-mail: huang.xiaodong@gene.com; Vishva Dixit,(dixit@gene.com)

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.

10.1038/cr.2016.31

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