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Deubiquitylating enzymes and drug discovery: emerging opportunities

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 knowled...

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Detalles Bibliográficos
Autores principales: Harrigan, Jeanine A., Jacq, Xavier, Martin, Niall M., Jackson, Stephen P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097658/
https://www.ncbi.nlm.nih.gov/pubmed/28959952
http://dx.doi.org/10.1038/nrd.2017.152
Descripción
Sumario: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. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrd.2017.152) contains supplementary material, which is available to authorized users.