rezatapopt + azacitidine

Rezatapopt + azacitidine is an investigational combination therapy under clinical evaluation for the treatment of myeloid malignancies, specifically acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) harboring the TP53 Y220C mutation. Rezatapopt is a first-in-class, orally available small molecule that selectively binds to and stabilizes the p53 Y220C mutant protein, restoring its wild-type tumor suppressor function. This reactivation of p53 leads to disruption of tumor progression in cancers with this specific mutation[2][4][6]. Azacitidine is a pyrimidine nucleoside analogue and demethylating agent that incorporates into RNA and DNA, inhibiting DNA methyltransferase activity, impairing DNA methylation, disrupting RNA metabolism, and inducing cytotoxicity in abnormal hematopoietic cells[3][8]. The combination aims to leverage both targeted reactivation of mutant p53 by rezatapopt and epigenetic modulation/cytotoxicity by azacitidine for synergistic anti-leukemic effects. The regimen is currently being studied in Phase I trials for patients with relapsed or refractory AML or MDS with TP53 Y220C mutations[1][7].