A5085723416- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- PARP inhibition in cancer therapy
- Andrographolide Research and Applications
- Inflammasome and immune disorders
- 14-3-3 protein interactions
University of Bonn
2022-2025
A novel class of USP7 PROTACs were designed and synthesized. CST967, a CRBN-based degrader, showed potent selective depletion leading to apoptosis in multiple cancer lines.
The development of von Hippel–Lindau (VHL) hijacking proteolysis-targeting chimeras (PROTACs) has been hindered by suboptimal physicochemical properties, including high total polar surface area (TPSA), hydrogen bond donor (HBD) counts, and poor solubility. This study explores a novel approach to enhance the characteristics VHL-recruiting USP7 degraders while maintaining their efficacy. By systematically optimizing lipophilicity, count, TPSA USP-targeting moieties, we designed series...
Abstract Naturally occurring compounds represent a vast pool of pharmacologically active entities. One such is andrographolide, which endowed with many beneficial properties, including the activity against severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2). To initiate drug repurposing or hit optimization campaign, it imperative to unravel primary mechanism(s) antiviral action andrographolide. Here, we showed by means reporter gene assay that andrographolide exerts its...
Abstract BACKGROUND Ependymomas (EPN) arise in the supratentorial brain (ST-EPN), posterior fossa (PF-EPN), or spinal cord (SP-EPN), children and adults. Among three molecular PF-EPN groups, PFAs are characterized by young median age at diagnosis, a balanced genome poor outcome. Recently, enhancer of zeste inhibiting protein (EZHIP) has been identified as potential driver PFAs. By EZH2, EZHIP prevents distribution epigenetic repressor mark H3K27me3. Without known enzymatic functions though,...
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 an ubiquitin-specific protease 7 (USP7) inhibitor scaffold to degrade USP7. The hit compound CST967 caused highly selective degradation of USP7 inhibited proliferation USP7-dependent cancer cells. We present the first degrader, which...