New drugs to block a cancer-driving pathway in KRAS-mutant tumors
Official title: Development of Quinoxaline Based IKKbeta Inhibitors for Kras Driven Cancers
Funded at University of Cincinnati · NIH-11424752 · Data updated 2026-11-12
Scientists are making and testing novel molecules to shut down a protein pathway that helps KRAS-mutant cancers grow, with a focus on hard-to-treat cancers like pancreatic cancer.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Cincinnati NIH-funded |
| Lab location | 1 site (Cincinnati, United States) |
| Project start | May 9, 2016 |
| Project end | June 30, 2028 |
| Funding year | 2025 |
| Award (this year) | $383,749 |
| NIH project number | 7R01CA197999-09 |
| Project ID | NIH-11424752 on NIH RePORTER |
Who could benefit from this research
✓Could help
People with KRAS-mutant tumors—especially those with pancreatic cancer—are the population who could be candidates for future clinical trials of a lead drug from this project.
✕Less likely to help
Patients whose cancers do not have KRAS mutations or whose disease is driven by unrelated pathways are unlikely to benefit from this specific approach.
What this research studies
Researchers are designing and improving small molecules and PROTAC compounds that target MAP3K1/IKKbeta signaling, a pathway that helps tumors grow. They will use cancer cell lines and tumor organoids to measure how the compounds affect tumor cells, and run RNA sequencing and proteome-wide screens to understand how the drugs work. The best compounds will be refined by changing linker chemistry and then tested in laboratory tumor models to check for anti-cancer activity. The goal is to pick a lead candidate with a clear mechanism of action for future development.
Why it matters
Potential benefit: If successful, this work could produce a new targeted treatment approach that slows tumor growth and spread in KRAS-driven cancers.
How similar studies have gone: Earlier IKKbeta inhibitors reached clinical trials but failed due to safety or lack of efficacy, while newer MAP3K1 inhibitors and PROTAC strategies are more recent and have shown promising preclinical activity but limited clinical proof so far.
Where this research is happening
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University of Cincinnati
Cincinnati, United States Active
Researchers
- Principal investigator: Natarajan, Amarnath (Amar) — University of Cincinnati
- Study coordinator: Natarajan, Amarnath (Amar)
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.