Introduction to proteolysis targeted chimeras (PROTACs): design principles, synthetic approaches, and applications

16 Apr

Dr. Jenny Desantis, Università degli Studi di Perugia

February 15-28, 2025

18 h, 3 CFU

Proteolysis targeting chimeras (PROTACs) represent an innovative class of compounds that are emerging in drug discovery and are opening the way to a next generation idea of therapeutic agents aimed at the removal of disease-related target proteins. Structurally, PROTACs are hetero-bifunctional molecules composed of two ligands, one binding the protein of interest (POI) and the other one recruiting an E3 ubiquitin ligase, concatenated through a linker. The chemically-induced formation of ternary complexes (POI-PROTAC-E3) leads to ubiquitination and proteasomal degradation of the target protein.

In this course, after an introduction to the principles used for PROTACs design and optimization, an overview of the different synthetic approaches exploited so far for the preparation of such tricky molecules will be presented. Furthermore, different examples of applications of PROTAC technology will be discussed.