Application
- Post-menopausal osteoporosis, osteoarthritis, and rheumatoid arthritis are three different musculoskeletal conditions that affect the bones and joints, often causing pain and mobility issues.
- Cathepsin K inhibitors regulate bone resorption in post-menopausal osteoporosis, slow down cartilage degradation in osteoarthritis, and modulate inflammatory processes in rheumatoid arthritis.
- Therefore, Cathepsin K is well-accepted as a valid drug target for those conditions. However, phase III clinical trials with odanacatib (a potent cathepsin K inhibitor by Merck and Co) for post-menopausal osteoporosis have failed due to adverse side effects.
Our Innovation
A potential treatment for musculoskeletal conditions, based on highly selective covalent irreversible inhibitors targeted to cathepsin K and selective covalent reversible and covalent irreversible activity-based probes.
A subset of the inhibitors we designed can be linked to targeting moiety to reduce adverse effects and therefore serves as candidate drugs for postmenopausal osteoporosis, osteoarthritis, and rheumatoid arthritis. In addition, the probes we developed enable monitoring of cathepsin K activity, in mouse and human samples ex vivo, and may potentially be used in vivo.
Advantages
- The highly specific covalent reversible probes can detect cathepsin K activity and then the probe quickly clears from the body, while the covalent irreversible strongly labels the active enzyme.
- Potential treatment while lowering the risk for side effects.
Opportunity
A combined package of chemical reagents for use as drugs as well as means to study the drug effectiveness and adverse effects during drug development.
We are seeking collaboration with pharma companies developing treatments for musculoskeletal conditions.
