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Cyclophosphamide, Doxorubicin, Hydralazine, and Magnesium Valproate combination therapy
- Development stage
- Unknown
- Lead developer
- Takeda
- Modality
- Nucleic Acid-Directed Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Classical Binding Small Molecules → Small Molecules
- Administration
- Oral, Intravenous
01
Overview
This combination therapy consists of two conventional chemotherapy agents (cyclophosphamide and doxorubicin) plus two epigenetic modifiers (hydralazine and magnesium valproate). Hydralazine acts as a DNA methylation inhibitor while magnesium valproate functions as a histone deacetylase (HDAC) inhibitor. Together, these epigenetic modifiers aim to reverse aberrant DNA methylation and histone deacetylation, which are common epigenetic alterations in cancer. The combination was studied in phase II clinical trials for locally advanced breast cancer, with patients receiving hydralazine and magnesium valproate starting 7 days before beginning conventional chemotherapy. It was generally well-tolerated, with common side effects including hematological toxicity (neutropenia, anemia), and transient drowsiness or depressed level of consciousness.
- Other names
- Epigenetic therapy + conventional chemotherapy
02
Targets
DNADNMT (DNA methyltransferase)TOP2A (DNA topoisomerase II)AcetylcholinesteraseHDAC (HDAC family)
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