Degrade the damaged p53 protein rather than trying to repair it
Some faulty p53 proteins do not just stop protecting the cell; they actively help the cancer. Removing them entirely may be easier than fixing them.
Gain-of-function mutant p53 accumulates to high levels because it escapes MDM2-mediated turnover, and it drives invasion and chemoresistance in mouse models. A selective degrader exploiting the mutant's dependence on HSP90 or its distinct conformation could deplete it. Precedent: HSP90 inhibitors destabilise mutant p53 and prolong survival in mutant-p53 mouse models, but are too toxic; a targeted degrader would separate the effect from global chaperone inhibition.
- The undruggable drivers · The proteins that drive most cancers, such as MYC, mutant p53 and most RAS variants, still have no good drug.
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not linked directly; found by shared links- 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.
- ProductEprenetapopt
Shares p53 / RB / cell-cycle checkpoint, TP53, The undruggable drivers.
- PersonShaomeng Wang
Shares PROTACs & molecular glues (targeted protein degradation), TP53.
- IdeaDrag cancer's surface and secreted proteins to the cell's recycling bin
Shares PROTACs & molecular glues (targeted protein degradation), The undruggable drivers.
- IdeaA guaranteed purchase prize for the first drug against a named hard target
Shares TP53, The undruggable drivers.
- IdeaInstruct tumour cells to make antibodies against their own oncoprotein
Shares PROTACs & molecular glues (targeted protein degradation), The undruggable drivers.
- IdeaMilestone prizes for first-in-class mechanisms reaching human proof of concept
Shares p53 / RB / cell-cycle checkpoint, TP53, The undruggable drivers.