Tools to Detect and Inhibit Protease Activity for Disease Management

Identifying the activity of specific molecular entities in diseases by molecular imaging may show the localization of pathologies, shed light on disease progression and suggest suitable treatments. The cysteine cathepsins proteases play key roles in several types of human diseases where they are highly active and serve as biomarkers and therapeutic targets. Thus, cathepsins also serve as excellent targets for molecular imaging.
Over the last decade, the Blum lab has been focusing on generating various types of selective activity-based probes (ABPs) targeted to specific cathepsins as tools to detect the activity of these enzymes in cells and in vivo. ABPs are small molecules designed to modify enzyme targets in an activity-dependent manner, covalently attaching a tag to their active site enabling the detection of enzyme activity. Data on various probes for cathepsin imaging and their applications in disease-setting will be described in the lecture. In addition, the use of cathepsin probes and inhibitors to detect and abrogate resistance to immunotherapy treatment will be presented.
In conclusion, the ABP technology is unique, it enables studying the involvement of enzyme activity in diseases and has the potential for clinical use.