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valproic acid + hydroxyurea + 6-mercaptopurine
- Development stage
- Unknown
- Lead developer
- Haukeland University Hospital
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
This combination therapy regimen is being investigated in the HUVAMER clinical trial at Haukeland University Hospital for the treatment of acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (HR-MDS). The regimen is specifically designed for patients who are considered unfit for standard intensive chemotherapy. It utilizes valproic acid (VPA), a histone deacetylase (HDAC) inhibitor originally used as an anticonvulsant, in combination with either hydroxyurea (HU) or 6-mercaptopurine (6-MP), both of which are established small molecule cytotoxic agents. Valproic acid acts as an epigenetic modulator, inducing histone acetylation and promoting cell differentiation and apoptosis in leukemic cells. Hydroxyurea synergizes with valproic acid by inhibiting ribonucleotide reductase and affecting DNA damage repair mechanisms, while 6-mercaptopurine acts as a purine antimetabolite. This Phase 1/2 approach focuses on providing a well-tolerated, oral, disease-stabilizing or palliative treatment option for elderly or frail patients.
- Other names
- VPA + HUVPA + 6-MPvalproic acid + hydroxycarbamidevalproic acid + 6-mercaptopurine
02
Targets
DNAPPAT (Amidophosphoribosyltransferase)RNR (Ribonucleotide reductase)HDAC (HDAC family)
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