Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery
2020; Cell Press; Volume: 181; Issue: 1 Linguagem: Inglês
10.1016/j.cell.2019.11.031
ISSN1097-4172
AutoresGeorge M. Burslem, Craig M. Crews,
Tópico(s)Peptidase Inhibition and Analysis
ResumoNew biological tools provide new techniques to probe fundamental biological processes. Here we describe the burgeoning field of proteolysis-targeting chimeras (PROTACs), which are capable of modulating protein concentrations at a post-translational level by co-opting the ubiquitin-proteasome system. We describe the PROTAC technology and its application to drug discovery and provide examples where PROTACs have enabled novel biological insights. Furthermore, we provide a workflow for PROTAC development and use and discuss the benefits and issues associated with PROTACs. Finally, we compare PROTAC-mediated protein-level modulation with other technologies, such as RNAi and genome editing.
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