{"entity":{"id":"mdm2-inhibitors","kind":"technology","name":"MDM2 inhibitors","aka":[],"tldr":"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.","status":"phase-3","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Mdm2","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mdm2"}],"tags":[],"related":[],"cancers":["aml","sarcoma"],"sections":["targeted-therapy"],"technologies":[],"targets":["mdm2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"notes":[],"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"]},"route":"/technologies/mdm2-inhibitors/","neighbours":{"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}],"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"target":[{"id":"mdm2","kind":"target","name":"MDM2","route":"/targets/mdm2/"}]}}