Hydralazine-valproate: a repositioned drug combination for the epigenetic therapy of cancer

Expert Opin Drug Metab Toxicol. 2014 Oct;10(10):1433-44. doi: 10.1517/17425255.2014.947263. Epub 2014 Aug 25.


Introduction: DNA methylation (DNMTi) and histone deacetylase inhibitors (HDACi) are in development for cancer therapy. So far, four epigenetic drugs are approved for myelodysplastic syndrome (MDS) and cutaneous T-cell lymphoma (CTCL). The combination of hydralazine-valproate (TRANSKRIP(™)) is being repositioned as an oral DNMT and HDAC inhibitor.

Areas covered: Brief discussion on the current status of epigenetic drugs and studies published on the preclinical and clinical development of the hydralazine-valproate combination.

Expert opinion: Drug repositioning is a strategy for prompt and cost-efficient drug discovery. There is evidence that combining DNMTi with HDACi would be more efficacious than administering each agent on its own. Hydralazine-valproate is safe when used alone or in combination with chemotherapy or chemoradiation. The fact that both drugs are orally administered is another advantage over current epigenetic drugs. This combination is promising but larger studies are needed. Among these, the randomized Phase III trials in advanced and in locally advanced cervical cancer combined with chemotherapy and cisplatin-radiation respectively, would eventually confirm its efficacy. Studies on MDS and CTCL would also eventually prove the efficacy of hydralazine valproate so that in the coming years hydralazine-valproate could have a role in cancer epigenetic therapy.

Keywords: cervical cancer; cutaneous T-cell lymphoma; drug repositioning; epigenetics; hydralazine; myelodysplastic syndrome; orphan drug; valproate.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Combined Modality Therapy
  • DNA Methylation / drug effects
  • Drug Repositioning
  • Epigenesis, Genetic
  • Histone Deacetylase Inhibitors / administration & dosage
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • Hydralazine / administration & dosage
  • Hydralazine / pharmacology
  • Hydralazine / therapeutic use*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Valproic Acid / administration & dosage
  • Valproic Acid / pharmacology
  • Valproic Acid / therapeutic use*


  • Histone Deacetylase Inhibitors
  • Hydralazine
  • Valproic Acid