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triapine + cytarabine
- Development stage
- Phase 1
- Lead developer
- Vion Pharmaceuticals
- Modality
- Small Molecules
- Administration
- Intravenous
01
Overview
Triapine + cytarabine is a combination of two investigational anticancer drugs used primarily in the treatment of acute myeloid leukemia (AML) and other relapsed or refractory leukemias. **Triapine** (3-aminopyridine-2-carboxaldehyde-thiosemicarbazone) is a potent small-molecule inhibitor of ribonucleotide reductase (RNR), an enzyme necessary for DNA synthesis and repair. **Cytarabine** (also known as ara-C) is an antimetabolite chemotherapeutic that is incorporated into DNA during replication, causing chain termination and apoptosis in proliferating cells. Triapine inhibits RNR, leading to depleted deoxynucleotide pools, which enhances the cytotoxic effects of cytarabine by promoting increased incorporation of cytarabine triphosphate (ara-CTP) into DNA of leukemic cells. The combination has demonstrated additive or synergistic cytotoxicity in preclinical and phase I studies, with activity observed in relapsed/refractory leukemia, though the combination is associated with toxicities such as methemoglobinemia (from triapine) and expected cytarabine-associated toxicities. The drugs are administered intravenously in a specific sequence to maximize biochemical modulation[1][2][4][5][3].
- Brand names
- Triapine + cytarabine
- Other names
- triapine + ara-C3-AP + ara-C
02
Targets
DNA polymerase familyRRM2
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