Eprenetapopt
Eprenetapopt (APR-246) was a drug meant to refold mutant p53, the most common broken protein in cancer. Its phase 3 in blood cancer failed in 2020.
Eprenetapopt (APR-246) is a prodrug of methylene quinuclidinone, proposed to covalently modify mutant p53 and restore wild-type conformation. Phase 2 with azacitidine in TP53-mutant MDS reported ~50% complete remission. The phase 3 (n=154) missed its primary endpoint of complete remission rate in 2020 (33% vs 22%, not significant). Aprea pivoted away. Subsequent studies suggest much of the activity reflected glutathione depletion and oxidative stress rather than p53 refolding.
Lesson: TP53 remains undrugged by direct reactivation; the field moved to mutation-specific correctors (rezatapopt for Y220C) and to exploiting p53-loss dependencies (WEE1, ATR).
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Latest papers
topQuery for this drug: (TITLE:"Eprenetapopt" OR ABSTRACT:"Eprenetapopt" OR TITLE:"APR-246" OR ABSTRACT:"APR-246") 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 Eprenetapopt, not a curated reading list.
Pages like this
not linked directly; found by shared links- IdeaDegrade the damaged p53 protein rather than trying to repair it
Shares p53 / RB / cell-cycle checkpoint, TP53, The undruggable drivers.
- IdeaExtend p53 reactivation beyond the Y220C mutation
Shares p53 / RB / cell-cycle checkpoint, TP53, The undruggable drivers.
- CompanyBulsara Bioworks
Shares p53 / RB / cell-cycle checkpoint, TP53.
- ProductTrastuzumab duocarmazine
Shares Failures are hidden and the tag failure.
- ProductMelphalan flufenamide
Shares Failures are hidden and the tag failure.
- ProductTusamitamab ravtansine
Shares Failures are hidden and the tag failure.
- TrialXPORT-EC-042 / ENGOT-EN20 / GOG-3083
Shares TP53 and the tag failure.
- ProductMagrolimab
Shares Failures are hidden, Acute myeloid leukaemia and the tag failure.