Biological Evaluation of Serine Protease Inhibitors and Inducers of Protein Degradation

Abstract

Serine proteases represent the largest group of enzymes of the human degradome. As such, they are valuable targets for the development of new drugs, due to their involvement in several diseases. Over the course of this work, a library of 73 compounds was evaluated as inhibitors of selected serine proteases. This way, several inhibitors of the enzyme matriptase-2, an important regulator of iron homeostasis, and thrombin were discovered. Some of these were established further for the use as activity-based probes in additional experiments. In a different approach, a test system for the evaluation of protein degradation inducing molecules (PROTACs) was conceptualized and established. Targeted protein degradation represents a promising new therapeutic option for the treatment of previously undruggable diseases.