Targeting the deubiquitinase USP7 for degradation with PROTACs.

Chem Commun (Camb)

Pharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121, Bonn, Germany.

Published: August 2022

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710854PMC
http://dx.doi.org/10.1039/d2cc02094gDOI Listing

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