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MDM2 is the protein that degrades p53; blocking it reactivates p53 in tumours where the gene is intact, especially the liposarcomas that carry extra copies of MDM2. This dossier gathers the 2 products (0 approved), 5 trials, 6 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
RING-domain E3 ligase that binds the p53 transactivation domain, ubiquitinates it for proteasomal degradation and exports it from the nucleus; p53 in turn transcribes MDM2 (negative feedback); MDMX (MDM4) is a heterodimer partner.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Sarcomas | 90% | MDM2 amplification in well/dedifferentiated liposarcoma | doi.org | |
| Gallbladder cancer | 12% | Amplification | Amplification in 29 of 244 samples, 11.9%, in cBioPortal gbc_mskcc_2022 and 12 of 103, 11.7%, in gbc_msk_2018; 6.5% across 1,254 biliary tract cancers of all sites (Cowzer 2026). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Modality | Phase 3 | Phase 2 |
|---|---|---|
| Small molecule 2 |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 2/3 | Recruiting | A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects With TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy | - | ||
| 2 | Active | A Phase II, Single-arm, Open-label, Long-term Safety Rollover Trial of Oral Brigimadlin in Patients With Solid Tumours | - | ||
| 2 | Active | A Two-Part, Randomized, Open-label, Multicenter, Phase 2a/2b Study of the Efficacy, Safety, and Pharmacokinetics of KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera | - | ||
| 1/2 | Recruiting | An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma or Relapsed/Refractory Chronic Lymphocytic Leukemia | - | ||
| 1/2 | Recruiting | A Phase 1/2a, Open-Label Study of Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SA53-OS, an MDM2 Inhibitor, in Patients With Locally Advanced or Metastatic p53 Wild-Type Solid Tumors | - | - |
No recorded escape route names this target.
KEGG's bladder cancer map shows two routes: low-grade papillary tumours driven by FGFR3 or HRAS activating the MAPK relay, and high-grade invasive tumours that lose TP53 and RB1. Erdafitinib targets the first route; antibody-drug conjugates and PD-1 antibodies now anchor treatment of the second.
Which nodes have drugs →This KEGG map shows the two genetic roads to glioblastoma: primary tumours amplify EGFR and lose PTEN and p16, secondary tumours from lower-grade astrocytomas over-express PDGF and CDK4 and lose TP53 and RB. It explains why growth-factor and cell-cycle drugs are the main targeted options in brain tumours, and why paediatric low-grade gliomas with BRAF changes respond to MAPK inhibitors.
Which nodes have drugs →KEGG's melanoma map shows BRAF or NRAS mutations driving the MAPK growth relay, PTEN loss driving PI3K/AKT, and loss of the CDKN2A brakes (p16 and p14ARF) on CDK4/6 and p53. BRAF plus MEK inhibitors and immune checkpoint antibodies have transformed treatment.
Which nodes have drugs →KEGG's prostate cancer map centres on the androgen receptor, the hormone switch that prostate cells depend on, plus loss of PTEN and NKX3.1 that lets PI3K/AKT growth signalling run free. Hormone therapy, AR antagonists and now AKT inhibitors act on these two arms.
Which nodes have drugs →p53 is the cell's emergency coordinator: DNA damage, oncogene stress or lack of oxygen switch it on, and it then pauses division, orders repairs, or triggers suicide or permanent retirement, while MDM2 keeps it off in healthy cells. About half of cancers mutate p53 outright, and sarcomas, gliomas, melanomas and retinoblastomas silence it instead by amplifying MDM2 or MDM4.
Which nodes have drugs →Cells tag unwanted proteins with a small marker called ubiquitin and feed them into a shredder, the proteasome. Myeloma cells, which make antibody in bulk, die if the shredder jams; and the newest drugs hijack the tagging machinery to make a cancer destroy its own oncoproteins.
Which nodes have drugs →No companion diagnostic in the registry measures this target.
No model entry for this target yet; check the cancer entries on the models page.
No open questions recorded for this target yet. Suggest one.
Query for this target: (TITLE:"MDM2" OR ABSTRACT:"MDM2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about MDM2, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/mdm2.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/mdm2.json. Licence CC BY-NC 4.0.