First-in-class Mdm2 PROTACs to treat cancers with mutant or missing p53
Official title: Design of the First Mdm2 Targeting PROTACs for treatment of p53 Mutant or Deficient Cancers
Funded at Wistar Institute · NIH-11378532 · Data updated 2026-11-12
A new treatment approach uses Mdm2-targeting PROTACs to remove Mdm2 from cancer cells that lack functional p53, aiming to kill cancer cells and work in living organisms.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Wistar Institute NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project start | September 7, 2022 |
| Project end | July 31, 2027 |
| Funding year | 2026 |
| Award (this year) | $547,167 |
| NIH project number | 5R01CA272645-05 |
| Project ID | NIH-11378532 on NIH RePORTER |
Who could benefit from this research
✓Could help
Patients whose cancers lack functional p53 (mutant or deleted) and express Mdm2 could be eligible in future development steps.
✕Less likely to help
Patients whose tumors rely on p53-independent pathways not affected by Mdm2 degradation may see limited benefit.
What this research studies
This project develops PROTAC molecules that specifically target and degrade Mdm2 in cancer cells without functional p53. The lead compounds show high binding affinity, promote Mdm2 degradation, and induce cancer cell death, with evidence of efficacy in animal models. The work also reports favorable safety, metabolic stability, and measurable exposure in mice to support in vivo efficacy testing. By disrupting Mdm2's p53-independent roles, the research aims to broaden treatment options for p53-deficient cancers. If successful, these compounds could become a new therapeutic strategy for tumors driven by Mdm2 activity.
Why it matters
Potential benefit: If successful, patients with p53-deficient cancers could have a new treatment that directly targets Mdm2, potentially slowing tumor growth and improving survival.
How similar studies have gone: Similar Mdm2-targeting strategies have shown preclinical promise, with proof-of-concept in model systems and some in vivo activity.
Where this research is happening
-
Wistar Institute
Philadelphia, United States Active
Researchers
- Principal investigator: Salvino, Joseph M — Wistar Institute
- Study coordinator: Salvino, Joseph M
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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.