Rezatapopt — Investigational Agent
Other · Phase 1/2 · PMV Pharmaceuticals
Mechanism of Action
Rezatapopt is an orally administered, small-molecule p53 reactivator that selectively binds a cryptic pocket created by the TP53 Y220C mutation. This specific missense mutation destabilizes the p53 DNA-binding domain; rezatapopt binds and stabilizes the mutant protein, restoring its wild-type conformation and transcriptional activity. Reactivated p53 drives expression of cell-cycle arrest and pro-apoptotic target genes, selectively eliminating Y220C-mutant malignant cells. In myeloid malignancies it is being combined with azacitidine to exploit complementary induction of apoptosis in…
Investigational Indications
- TP53 Y220C-mutant acute myeloid leukemia
- TP53 Y220C-mutant myelodysplastic syndrome
- TP53 Y220C-mutant solid tumors