Issue 63, 2022

Targeting the deubiquitinase USP7 for degradation with PROTACs

Abstract

Targeting deubiquitinating enzymes (DUBs) has emerged as a promising therapeutic approach in several human cancers and other diseases. DUB inhibitors are exciting pharmacological tools but often exhibit limited cellular potency. Here we report PROTACs based on a ubiquitin-specific protease 7 (USP7) inhibitor scaffold to degrade USP7. By investigating several linker and E3 ligand types, including novel cereblon recruiters, we discovered a highly selective USP7 degrader tool compound that induced apoptosis of USP7-dependent cancer cells. This work represents one of the first DUB degraders and unlocks a new drug target class for protein degradation.

Graphical abstract: Targeting the deubiquitinase USP7 for degradation with PROTACs

Supplementary files

Article information

Article type
Communication
Submitted
15 Apr 2022
Accepted
07 Jul 2022
First published
13 Jul 2022

Chem. Commun., 2022,58, 8858-8861

Targeting the deubiquitinase USP7 for degradation with PROTACs

A. Murgai, I. Sosič, M. Gobec, P. Lemnitzer, M. Proj, S. Wittenburg, R. Voget, M. Gütschow, J. Krönke and C. Steinebach, Chem. Commun., 2022, 58, 8858 DOI: 10.1039/D2CC02094G

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