Targeting the Hck and Fgr enzymes in acute myeloid leukemia
Discovery and Development of Allosteric Inhibitors of Src-family Kinases for AML
Researchers are creating new drugs that bind to parts of the Hck and Fgr enzymes to try to stop AML cells from growing and to prevent drug resistance in people with acute myeloid leukemia.
Quick facts
| Grant type | R21 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-11309106 on NIH RePORTER |
What this research studies
This project is designing molecules that attach to non‑active parts of two enzymes (Hck and Fgr) that are often overactive in AML patient bone marrow. The team will screen compounds, study how they bind using structural and biochemical tests, and test promising molecules on AML cells and in mouse models. They will also explore combining these new allosteric compounds with existing ATP‑site inhibitors to reduce the chance cancer cells become drug resistant. The work is being carried out in the lab at the University of Pittsburgh and is focused on early drug discovery rather than a patient trial at this time.
Who could benefit from this research
Good fit: People with acute myeloid leukemia, especially those whose bone marrow shows high Hck or Fgr levels or who have developed resistance to current kinase inhibitors, would be most likely to benefit down the line.
Not a fit: Patients with other types of cancer or AML driven by unrelated pathways are unlikely to benefit directly from this early laboratory work.
Why it matters
Potential benefit: If successful, this work could lead to new, more selective AML treatments that work when current kinase inhibitors fail and help prevent resistance.
How similar studies have performed: A similar allosteric-plus-ATP inhibitor approach succeeded in preventing resistance in Bcr‑Abl models for CML (asciminib plus nilotinib), but allosteric targeting of Hck/Fgr in AML is largely untested.
Where this research is happening
Pittsburgh, United States
- University of Pittsburgh at Pittsburgh — Pittsburgh, United States (Active)
Researchers
- Principal investigator: Smithgall, Thomas E. — University of Pittsburgh at Pittsburgh
- Study coordinator: Smithgall, Thomas E.
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.