How drugs target the KRAS G12C cancer mutation
KRAS G12C: Kinetic and Redox Characterization of Covalent Inhibition
This project looks at how two drugs attach to and act on the KRAS G12C mutation so treatments for people with KRAS G12C cancers can be improved.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Univ of North Carolina Chapel Hill NIH-funded |
| Lab location | 1 site (Chapel Hill, United States) |
| Project ID | NIH-11295398 on NIH RePORTER |
What this research studies
Researchers use a new fluorescence-based lab method to measure how acrylamide-based drugs bind and react with the KRAS G12C protein. They directly compare the kinetics of the two clinical compounds sotorasib (AMG510) and adagrasib (MRTX849) to understand their different behaviors. The team also examines how the oxidative (redox) state inside tumor cells affects the reactive cysteine at position 12 and drug binding. Results come from biochemical assays and cell-based experiments that aim to explain why drugs differ and how to design better ones.
Who could benefit from this research
Good fit: People whose tumors carry the KRAS G12C mutation (for example many non-small cell lung cancers) are the group most likely to benefit from this research.
Not a fit: Patients whose cancers do not have the KRAS G12C mutation or whose tumors rely on other resistance mechanisms are unlikely to receive direct benefit from this specific work.
Why it matters
Potential benefit: If successful, this work could guide improved KRAS G12C-targeted drugs or better use of existing drugs for patients with KRAS G12C-positive tumors.
How similar studies have performed: Covalent KRAS G12C inhibitors such as sotorasib and adagrasib have already shown clinical benefit, but detailed kinetic and redox analyses like this are relatively new.
Where this research is happening
Chapel Hill, United States
- Univ of North Carolina Chapel Hill — Chapel Hill, United States (Active)
Researchers
- Principal investigator: Campbell, Sharon L — Univ of North Carolina Chapel Hill
- Study coordinator: Campbell, Sharon L
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.