HKI 46F08, a novel potent histone deacetylase inhibitor, exhibits antitumoral activity against embryonic childhood cancer cells

Anticancer Drugs. 2008 Oct;19(9):849-57. doi: 10.1097/CAD.0b013e32830efbeb.


Embryonic childhood cancer such as neuroblastoma and medulloblastoma are still a therapeutic challenge requiring novel treatment approaches. Here, we investigated the antitumoral effects of HKI 46F08, a novel trifluoromethyl ketone histone deacetylase (HDAC) inhibitor with a nonhydroxamic acid type structure. HKI 46F08 inhibits in-vitro HDAC activity in cell-free assays with a half maximal inhibitory concentration of 0.6 micromol/l and intracellular HDAC activity with a half maximal inhibitory concentration of 1.8 micromol/l. The compound reduces viability of both cultured neuroblastoma and medulloblastoma cells with an EC50 of 0.1-4 micromol/l. HKI 46F08 efficiently arrests tumor cell proliferation, represses clonogenic growth and induces differentiation and apoptosis in both MYCN-amplified and nonamplified neuroblastoma cells. In summary, we identified HKI 48F08 as a structural novel, potent HDAC inhibitor with strong antitumoral activity against embryonic childhood cancer cells in the low micromolar range.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Benzimidazoles / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / pharmacology*
  • Histone Deacetylase Inhibitors*
  • Humans
  • Medulloblastoma / drug therapy*
  • Neuroblastoma / drug therapy*
  • Rats


  • Antineoplastic Agents
  • Benzimidazoles
  • Enzyme Inhibitors
  • HKI 46F08
  • Histone Deacetylase Inhibitors