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Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery.

ABSTRACT: New 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.

SUBMITTER: Burslem GM

PROVIDER: S-EPMC7319047 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery.

Burslem George M GM Crews Craig M CM

Cell 20200116 1

New 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 develo ...[more]

PMID: 31955850

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