# MDM2 inhibitors

Source: https://onco.cc/technologies/mdm2-inhibitors/  
OnCo record `mdm2-inhibitors` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Drugs that stop MDM2 destroying p53, reawakening the cell's guardian protein in tumours where p53 is intact but suppressed, such as some sarcomas and leukaemias.

## Summary

MDM2 tags the tumour suppressor p53 for degradation, and MDM2 amplification is the hallmark of liposarcoma and other tumours that keep wild-type p53. Small molecules that block the MDM2-p53 interaction (idasanutlin, milademetan, navtemadlin, brigimadlin) restore p53 and cause cell-cycle arrest and death. Trials in acute myeloid leukaemia and liposarcoma have shown activity but also thrombocytopenia and gastrointestinal toxicity, and no agent is approved; combinations and intermittent dosing are being tested.

## Fields

- Kind: Technology
- Status: phase-3
- Last checked: 2026-09-04
- Principle: Inhibitors occupy the p53-binding pocket of MDM2, stabilising p53 so it can trigger apoptosis or senescence in cells with wild-type TP53.
- Strengths: Reactivates a non-mutated tumour suppressor; Biomarker-defined populations
- Limitations: Thrombocytopenia and gut toxicity; Only in TP53 wild-type tumours; No approval after several phase 3 trials

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Mdm2
- Wikipedia: https://en.wikipedia.org/wiki/Mdm2

## Connected records

- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/)
- fronts: [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- targets: [MDM2](https://onco.cc/targets/mdm2/)

---
JSON: https://onco.cc/api/v1/entities/mdm2-inhibitors.json