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azacitidine + birinapant
- Development stage
- Phase 2
- Lead developer
- Medivir
- Modality
- Small Molecules
- Administration
- Intravenous, Subcutaneous
01
Overview
azacitidine + birinapant is an investigational drug combination comprising azacitidine, a hypomethylating agent (DNA methyltransferase inhibitor), and birinapant, a second mitochondrial-derived activator of caspases (SMAC) mimetic, which acts as an antagonist of inhibitor of apoptosis proteins (IAPs). Azacitidine is FDA-approved for myelodysplastic syndromes (MDS) and acts by reversing DNA methylation. Birinapant promotes apoptosis by degrading cIAP1 and cIAP2, thereby modulating apoptosis pathways. In studies, the combination has shown synergistic antileukemic activity, particularly in acute myeloid leukemia (AML) and MDS, including in patients naïve, refractory, or relapsed to HMAs. The combination augments apoptosis in AML/MDS stem and progenitor cells, showing promising preclinical and early clinical efficacy, but remains experimental[1][2][4][5].
- Other names
- 5-azacitidine + birinapant5-azacytidine + TL32711
02
Targets
DNMT1 (DNA (cytosine-5)-methyltransferase 1)DNMT3A (DNA methyltransferase 3 alpha)DNMT3B (DNA (cytosine-5)-methyltransferase 3B)XIAPBIRC2 (Cellular inhibitor of apoptosis protein 1)BIRC3 (Baculoviral IAP repeat-containing protein 3)
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