DEGRON · Tailored technologies for the development of next-generation PROTAC molecules (DEGRON)

PROTACs (Proteolysis-Targeting Chimeras) are a groundbreaking class of novel therapeutics capable of targeting disease-causing proteins previously thought to be undruggable. They work by recruiting E3 ligases to ubiquitinate target proteins, leading to their degradation. However, despite their promise, current PROTAC design is severely limited, relying on only two out of 613 E3 ligases. In addition, PROTAC development remains slow, inefficient and heavily reliant on trial-and-error approaches.The DEGRON project aims to revolutionize PROTAC drug discovery by commercializing key innovations originally developed in our ERC Starting Grant. First, we developed a patented high-throughput screening system to systematically identify the optimal E3 ligase for any given PROTAC target, enabling rational drug design. Second, we established real-time in vivo systems that enable target validation and precise measurement of PROTAC activity, replacing inefficient endpoint assays and reducing animal use and costs by over 70%. These innovations lay the foundation for a scalable drug discovery platform that transforms PROTAC development into a systematic and predictive process.Our commercialization strategy is two-pronged:1. Provision of DEGRON services: We plan to establish a company offering PROTAC screening and validation assays to both academic and industrial customers. Over time, our goal is to offer the full PROTAC development pipeline as a one-stop-shop.2. Development of proprietary PROTACs: We are currently advancing our own PROTAC pipeline under an ERC Consolidator Grant, focusing on therapeutics for pancreatic cancer. These preclinical candidates will be integrated and further developed within DEGRON and progressed towards clinical application. This ERC-PoC study will facilitate the establishment of a spin-off company that integrates E3 ligase discovery, PROTAC validation and drug development to set a new standard in targeted protein degradation-based medicine.