The field of Targeted Protein Degradation (TPD) has emerged as a new therapeutic modality to harness the ubiquitin-proteasome system for targeting proteins that were once considered undruggable through the traditional inhibitor-based modalities. 

TPD primarily relies on heterobifunctional molecules like proteolysis-targeting chimeras (PROTACs) and molecular glues to bring the target proteins into proximity to the ubiquitin-proteasome system to induce protein degradation. 

Molecular glues are monovalent small molecules with drug-like properties that alter the protein binding surface of E3 ligase, resulting in novel E3 ligase and target protein interactions. Molecular glues are difficult to design and are often discovered retrospectively. 

The rational design and discovery of molecular glues require an untargeted approach to understand the protein ternary complexes, target protein degradation, and ubiquitination induced by potential molecular glues. 

We have leveraged untargeted, high-throughput proteomic approaches to better understand protein-protein interactions and target protein degradation induced by prospective molecular glues. 

The recent developments in the field of high-throughput proteomics due to the introduction of faster and more sensitive mass spectrometers have brought us closer to the rational design and discovery of molecular glues.

Webinar learning objectives:

• The use of mass spectrometry to perform Targeted Protein Degradation (TPD) studies.
• Use of high-throughput proteomic approaches to better understand protein-protein interactions and target protein degradation induced by prospective molecular glues.
• Learn about the novel Orbitrap Astral Mass Spectrometer and it's capabilities.