Harnessing novel E3 ligases for cancer-specific degradation of oncogenic targets by PROTACs (B01)

• Subject Area: Cell Biology ; Hematology, Oncology ; Pharmacy
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 514894665

Proteolysis targeting chimeras (PROTACs) are a novel class of drugs that recruit E3 ubiquitin ligases to proteins to induce their degradation. To date, most PROTACs harness E3 ligases that are commonly expressed in healthy tissues and are not essential for tumor cells, making them less suitable as tumor therapeutics. We aim to identify E3 ligases that are expressed at low levels in healthy tissues to enable the development of a new generation of anti-cancer PROTACs that induce less therapy-induced toxicity. We will use a combination of genetic screening, novel cellular assays, structural biology and medicinal chemistry to identify and exploit the most suitable E3 ligases for PROTACs that are particularly active in tumor cells of the four tumor types being investigated in this consortium.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 387: Functionalizing the Ubiquitin System against Cancer - UbiQancer
• Applicant Institution: Technische Universität München (TUM)
• Project Heads: Professor Dr. Hermann Schindelin; Professor Dr. Elmar Wolf