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

Item Type:Article
Title:HKI 46F08, a novel potent histone deacetylase inhibitor, exhibits antitumoral activity against embryonic childhood cancer cells
Creators Name:Wegener, D. and Deubzer, H.E. and Oehme, I. and Milde, T. and Hildmann, C. and Schwienhorst, A. and Witt, O.
Abstract: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.
Keywords:Histone Deacetylase Inhibitor, HKI 46F08, Medulloblastoma, Neuroblastoma, Animals, Rats
Source:Anti-Cancer Drugs
ISSN:0959-4973
Publisher:Lippincott Williams & Wilkins (U.S.A.)
Volume:19
Number:9
Page Range:849-857
Date:October 2008
Official Publication:https://doi.org/10.1097/CAD.0b013e32830efbeb
PubMed:View item in PubMed

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