Carola Sparn/Birgitta Leuthner, Merck, Darmstadt
Targeted protein degradation can remove disease-causing proteins from the organism by hijacking the cells own proteasomal degradation mechanism. Thus, it is an attractive therapeutic option whenever mere inhibition of the activity of a target is not sufficient or achievable. Therefore, also targets can be addressed, which as yet have been classified undruggable. It is no surprise that this new modality is evolving fast across many therapeutic areas. At Merck Healthcare KGaA targeted protein degradation is an integral part of our drug discovery pipeline activities to enable us to bring more drugs to more patients. Due to the complex interplay of binding, enzymatic and functional events in the degrader mechanism there is a demand for a tailored assay suite to identify, characterize and optimize active compounds. Here, we are focusing on two different modalities, the bifunctional degraders and the molecular glue degraders. This talk will give an insight into how biochemical as well as cell-based assays are utilized to screen in-house libraries for the identification and characterization of new degraders and the optimization of our early bifunctional PROTACs to effective eliminators of drug targets.
