alvocidib + decitabine

Alvocidib + decitabine is an investigational combination therapy composed of alvocidib, a small-molecule cyclin-dependent kinase 9 (CDK9) inhibitor, and decitabine, a nucleoside analog DNA methyltransferase inhibitor. The combination is being studied for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), with the rationale that decitabine-mediated DNA hypomethylation sensitizes cells to apoptosis by inducing NOXA (an antagonist of the anti-apoptotic protein MCL-1), while alvocidib downregulates MCL-1 expression by inhibiting CDK9, potentially leading to synergistic antileukemic activity in MCL-1-dependent malignancies[5]. Clinical trials have explored this sequential regimen in relapsed/refractory and frontline settings for AML and MDS[1][4][5].