Finding new drugs to block resistant BTK in B-cell cancers
Cell-Based HTS Campaign to Identify Negative Allosteric Modulators of the Leukemia-associated Tyrosine Kinase, BTK”.
Using cell-based screening to find drugs that block the BTK protein for adults with B‑cell cancers such as chronic lymphocytic leukemia (CLL) who no longer respond to current BTK drugs.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Pittsburgh at Pittsburgh NIH-funded |
| Lab location | 1 site (Pittsburgh, United States) |
| Project ID | NIH-11248044 on NIH RePORTER |
What this research studies
Researchers will run high-throughput, cell-based screens to find small molecules that bind BTK away from its active site and reduce its activity. The team aims to identify negative allosteric modulators that can work even when common resistance mutations (like C481S and T474 changes) prevent current drugs from binding. Compounds found in the screen will be profiled in cellular models of B‑cell malignancies to pick leads for further development. This work is laboratory-based at the University of Pittsburgh and focuses on creating new drug candidates rather than immediate patient treatment.
Who could benefit from this research
Good fit: Adults with B‑cell malignancies such as CLL who have relapsed on or developed resistance to current BTK inhibitors, or who cannot tolerate those drugs, would be the likely eventual candidates.
Not a fit: Patients with cancers not driven by BTK, people seeking an immediate therapy option, or those expecting clinical enrollment now are unlikely to benefit from this preclinical screening project.
Why it matters
Potential benefit: If successful, this could produce new medicines that work for patients whose B‑cell cancers no longer respond to current BTK inhibitors and might reduce treatment discontinuations from side effects.
How similar studies have performed: Current BTK inhibitors like ibrutinib have helped many patients but resistance is common, and allosteric BTK targeting is a newer, less clinically proven approach.
Where this research is happening
Pittsburgh, United States
- University of Pittsburgh at Pittsburgh — Pittsburgh, United States (Active)
Researchers
- Principal investigator: Johnston, Paul a. — University of Pittsburgh at Pittsburgh
- Study coordinator: Johnston, Paul a.
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.