Blocking DDI2 to help proteasome-based cancer drugs work better
Identification of small molecule inhibitors of the DDI2 protease
Researchers are looking for small molecule drugs that block a protein called DDI2 so proteasome-targeting cancer treatments work better for people with cancers like multiple myeloma and some breast cancers.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Virginia Commonwealth University NIH-funded |
| Lab location | 1 site (Richmond, United States) |
| Project ID | NIH-11302659 on NIH RePORTER |
What this research studies
This project aims to find small molecules that bind and inhibit the DDI2 protease, a protein that activates a recovery program in cancer cells after proteasome-blocking drugs. The team will produce DDI2 protein in the lab and run large-scale screens using a protein thermal shift assay to spot compounds that stick to DDI2. Promising hits will go through follow-up laboratory tests and profiling to confirm activity and specificity, and top candidates will be tested in cell and animal tumor models to see if they boost existing proteasome therapies or slow tumor growth on their own. The work is preclinical but could lead to new drugs combined with current proteasome inhibitors or used as single agents.
Who could benefit from this research
Good fit: Patients with cancers commonly treated with proteasome inhibitors—such as multiple myeloma—or with tumors shown to depend on proteasome activity would be the most relevant candidates for future trials.
Not a fit: Patients without proteasome-dependent cancers or those needing immediate clinical treatment are unlikely to benefit from this early laboratory-focused work.
Why it matters
Potential benefit: If successful, DDI2 inhibitors could make existing proteasome-targeting therapies more effective and might also slow tumor growth as standalone treatments.
How similar studies have performed: Previous laboratory and animal studies show that lowering NRF1 or DDI2 can slow tumor growth and enhance proteasome inhibitor effects, but small-molecule DDI2 inhibitors are a novel approach.
Where this research is happening
Richmond, United States
- Virginia Commonwealth University — Richmond, United States (Active)
Researchers
- Principal investigator: Radhakrishnan, Senthil Kumar — Virginia Commonwealth University
- Study coordinator: Radhakrishnan, Senthil Kumar
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.