Large-scale Exploration of the Cereblon Neosubstrate Space
- Molecular Glue Degrader (MGD) discovery mostly relies on screening-based approaches, such as cell viability assays
- However, one limitation of such screening methods is the risk of overlooking week degraders and non-essential neosubstrates
- To address this risk, we developed a high throughput deep proteomics screening platform utilizing label-free, data-independent acquisition mass spectrometry for integrated proteomics and “ubiquitinomics” analysis
- Extensive analysis of the screening data and learnings from our initial MGD library were deployed into the development of our second-generation MGL. v2, which now contains well over 5,000 compounds
- The library has been screened by high-throughput proteomics, and the general performance of the MGL.v2 and the screening method, as well as the discovery of novel cereblon neosubstrates will be discussed