From Discovery to Bedside: Targeting the Ubiquitin System

Ingrid E Wertz; Xiaojing Wang

doi:10.1016/j.chembiol.2018.10.022

From Discovery to Bedside: Targeting the Ubiquitin System

Cell Chem Biol. 2019 Feb 21;26(2):156-177. doi: 10.1016/j.chembiol.2018.10.022. Epub 2018 Dec 13.

Authors

Ingrid E Wertz¹, Xiaojing Wang²

Affiliations

¹ Departments of Molecular Oncology and Early Discovery Biochemistry, Genentech, Inc., South San Francisco, CA 94008, USA. Electronic address: ingrid@gene.com.
² Department of Discovery Chemistry, Genentech, Inc., South San Francisco, CA 94008, USA.

PMID: 30554913
DOI: 10.1016/j.chembiol.2018.10.022

Abstract

The ubiquitin/proteasome system is a primary conduit for selective intracellular protein degradation. Since its discovery over 30 years ago, this highly regulated system continues to be an active research area for drug discovery that is exemplified by several approved drugs. Here we review compounds in preclinical testing, clinical trials, and approved drugs, with the aim of highlighting innovative discoveries and breakthrough therapies that target the ubiquitin system.

Keywords: DUB; E3; degradation; deubiquitinase; proteasome; ubiquitin; ubiquitin ligase.

Publication types

Review

MeSH terms

Drug Evaluation, Preclinical
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / metabolism
Humans
Proteasome Endopeptidase Complex / metabolism*
Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors
Proto-Oncogene Proteins c-mdm2 / metabolism
Ubiquitin / chemistry
Ubiquitin / metabolism*
Ubiquitin-Activating Enzymes / chemistry
Ubiquitin-Activating Enzymes / metabolism
Ubiquitin-Conjugating Enzymes / chemistry
Ubiquitin-Conjugating Enzymes / metabolism
Ubiquitin-Protein Ligases / chemistry
Ubiquitin-Protein Ligases / metabolism
Ubiquitination

Substances

Enzyme Inhibitors
Ubiquitin
Ubiquitin-Conjugating Enzymes
Proto-Oncogene Proteins c-mdm2
Ubiquitin-Protein Ligases
Proteasome Endopeptidase Complex
Ubiquitin-Activating Enzymes