Design of potent and selective USP25 and USP28 inhibitors (B06)

• Subject Area: Biochemistry ; Structural Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 514894665

Inhibition of USP28 and USP25 holds great promise for the pharmacological treatment of different cancers. However, the use of currently available small molecule inhibitors is limited due to their lack of selectivity bearing significant potential for serious side effects. To create potent and highly selective USP28 and USP25 inhibitors we will screen in parallel for novel binding sites for new chemical entities and characterize existing inhibitors. Hits will be iteratively optimized by rational Medicinal Chemistry methods, tightly guided by structural and biochemical characterization. Resulting potent and selective candidate compounds will be characterized for target engagement and cancer-specific anti-proliferative effects in selected cellular and in vivo models.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 387: Functionalizing the Ubiquitin System against Cancer - UbiQancer
• Applicant Institution: Technische Universität München (TUM)
• Project Heads: Professorin Dr. Caroline Kisker; Professor Dr. Eugen Proschak