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Drug intelligence / Profile preview
decitabine + valproic acid
- Development stage
- Phase 2
- Lead developer
- University of Texas MD Anderson Cancer Center
- Modality
- Classical Binding Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules
- Administration
- Intravenous, Oral, Subcutaneous
01
Overview
Decitabine + valproic acid is an investigational combination therapy consisting of decitabine, a DNA hypomethylating agent, and valproic acid, a histone deacetylase inhibitor. This combination is being studied primarily for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), particularly in elderly or relapsed/refractory patients. Decitabine inhibits DNA methyltransferase enzymes leading to hypomethylation of DNA and reactivation of silenced genes involved in cell cycle regulation and apoptosis. Valproic acid increases acetylation of histones by inhibiting histone deacetylases (HDACs), resulting in more transcriptionally active chromatin states. The rationale for combining these agents is that simultaneous inhibition of DNA methylation and HDAC activity can synergistically reactivate tumor suppressor genes silenced by epigenetic mechanisms[5][9]. Clinical studies have shown this combination induces objective responses in AML/MDS with manageable toxicity profiles; however, dose-limiting encephalopathy has been observed at higher doses of valproic acid[3][9].
- Other names
- decitabine and valproic acid5-aza-2'-deoxycytidine + VPA
02
Targets
DNMT1 (DNA (cytosine-5)-methyltransferase 1)HDAC (HDAC family)
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