Deubiquitylating enzymes and drug discovery: emerging opportunities
Nature Reviews Drug Discovery
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Harrigan, J., Jacq, X., Martin, N., & Jackson, S. (2018). Deubiquitylating enzymes and drug discovery: emerging opportunities. Nature Reviews Drug Discovery, 17 57-78. https://doi.org/10.1038/nrd.2017.152
More than a decade after a Nobel Prize was awarded for the discovery of the ubiquitin-proteasome system and clinical approval of proteasome and ubiquitin E3 ligase inhibitors, first-generation deubiquitylating enzyme (DUB) inhibitors are now approaching clinical trials. However, although our knowledge of the physiological and pathophysiological roles of DUBs has evolved tremendously, the clinical development of selective DUB inhibitors has been challenging. In this Review, we discuss these issues and highlight recent advances in our understanding of DUB enzymology and biology as well as technological improvements that have contributed to the current interest in DUBs as therapeutic targets in diseases ranging from oncology to neurodegeneration.
cancer, drug discovery, infectious diseases, inflammation, neurodegenerative diseases, ubiquitylation
The authors thank L. Greger for the generation of the phylogenic tree. Research in the S.P.J. laboratory is funded by the Cancer Research UK (CRUK) Program Grant C6/A18796 and a Wellcome Trust Investigator Award (206388/Z/17/Z), and institute core infrastructure funding is provided by the CRUK (C6946/A24843) and the Wellcome Trust (WT203144).
Cancer Research UK (18796)
Wellcome Trust (206388/Z/17/Z)
Cancer Research UK (C6946/A24843)
Wellcome Trust (203144/Z/16/Z)
External DOI: https://doi.org/10.1038/nrd.2017.152
This record's URL: https://www.repository.cam.ac.uk/handle/1810/267776