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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).
Converted to MQ, which alkylates cysteines in mutant p53 (claimed) and depletes glutathione. Connects to TP53.
1.Eprenetapopt slips into a pocket on TP53.
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Query 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.
Shares TP53 and the tag failure.
Shares Failures are hidden, Acute myeloid leukaemia and the tag failure.
Shares Failures are hidden and the tag failure.
Shares Failures are hidden and the tag failure.
Shares Failures are hidden and the tag failure.
Shares Failures are hidden and the tag failure.
Shares Failures are hidden and the tag failure.
Shares Failures are hidden and the tag failure.