APR-246 + venetoclax + azacitidine

A **combination therapy** of three agents: APR-246 (also known as eprenetapopt/PRIMA-1MET), venetoclax, and azacitidine. - **APR-246** is a first-in-class small molecule designed to restore wild-type function to mutant p53 protein, most notably in hematologic malignancies with TP53 mutations. It is converted into methylene quinuclidinone (MQ), which covalently binds mutant p53, refolding and reactivating its tumor suppressor function. It also has p53-independent effects via redox modulation and induction of oxidative stress[5][1]. - **Venetoclax** is a selective small molecule BCL-2 inhibitor that promotes apoptosis in tumor cells that are dependent on BCL-2 for survival. - **Azacitidine** is a nucleoside metabolic inhibitor/DNA methyltransferase inhibitor that integrates into DNA/RNA and inhibits methylation, restoring normal gene expression and promoting cytotoxicity, especially in myeloid malignancies like MDS and AML[2][6][4]. This triple regimen is under investigation particularly for TP53-mutant myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), building on preclinical and clinical synergy between APR-246 and azacitidine, and the established effectiveness of venetoclax + azacitidine in these diseases[5].

Other names

azacitidinevenetoclax