Over the last two decades, targeted protein degradation (TPD) by monovalent (molecular glues) or heterobifunctional degraders (PROTACs) has greatly advanced as a new therapeutic modality. This set of Best Practices covers the essential concepts and approaches to develop PROTACs.
- Part 1A introduces the ubiquitin-proteasome system (UPS) and its components, the mode of action and design of PROTACs to hijack the UPS to degrade a protein of interest (PoI)
- Part 1B describes commonly used assays for assessing and optimizing PROTACs, highlights the importance of the formation of a ternary complex and explains the concept of cooperativity.
- Part 1C deals with the challenges in PROTAC optimization as chemical probes or as drug candidates (ADME, bioavailability, safety), followed by two examples and a current overview of PROTACs in clinical trials.
The material (webinars, slide decks and case studies) is freely accessible for personal use or for use in further training or teaching material.
