Novel 20S proteasome inhibitors

The proteasome is a central component of the protein degradation machinery in eukaryotic cells and plays a role in regulating cell cycle, neoplastic growth and metastasis. Disruption of this degradative process with small molecule inhibitors against one or more catalytic subunits has implications in a number of human diseases such as cancer, inflammation and ischemic stroke and has exposed the proteasome as an important therapeutic target. Three proteasome inhibitors have so far received regulatory approval: bortezomib, carfilzomib and ixazomib. However, since primary resistance to proteasome inhibitors remains a challenge in patients, there is a continued need for new and/or improved proteasome inhibitors.