pevonedistat + venetoclax + azacitidine

This agent is a **combination therapy composed of three small molecules: pevonedistat, venetoclax, and azacitidine.** - **Pevonedistat** is a first-in-class, small-molecule inhibitor of the NEDD8-activating enzyme (NAE). By inhibiting NAE, pevonedistat disrupts protein neddylation, leading to upregulation of the pro-apoptotic protein NOXA and neutralization of MCL1, which in turn facilitates apoptosis in malignant cells[4][5]. - **Venetoclax** is a selective BCL-2 inhibitor that promotes apoptosis by blocking the anti-apoptotic effects of BCL-2, a key survival protein in leukemia cells[2][4]. - **Azacitidine** is a hypomethylating agent that incorporates into DNA and RNA, leading to cytotoxicity in abnormal hematopoietic cells and restoration of normal gene expression[2][4]. This combination is aimed at enhancing efficacy and overcoming resistance observed with azacitidine and venetoclax doublet regimens, particularly in **acute myeloid leukemia (AML)** and **myelodysplastic syndromes (MDS)**, especially in older patients and those with relapsed or refractory disease. The regimen has been evaluated in phase 1 and phase 2 trials for novel activity and tolerability, with preliminary results indicating safety and promising hematologic responses[1][4][5][2][3].

Other names

azacitidine + venetoclax + pevonedistattriplet therapy of pevonedistat, venetoclax and azacitidine