Deubiquitylating enzymes and drug discovery: emerging opportunities
Jeanine A Harrigan1, Xavier Jacq1, Niall M Martin1,2
1Mission Therapeutics Ltd, Moneta, Babraham Research Campus, Cambridge CB22 3AT, UK.
Abstract:
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.
More Related Videos
Related Concept Videos
Drug Discovery: Overview
Targets for Drug Action: Overview
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Drug Biotransformation: Overview
Drug Biotransformation: Overview
Drug Metabolism: Phase II Reactions
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....


