Novel valproic acid derivatives with potent differentiation-inducing activity in myeloid leukemia cells

Leukemia Research
Hedwig DeubzerOlaf Witt

Abstract

The anti-epileptic drug valproic acid harbors anti-tumoral activity in solid and leukemic tumor cell models and is currently evaluated in clinical trials. However, the plasma trough concentrations obtained in patients by common anti-epileptic dose regimens are below concentrations required for exerting anti-tumor effects in vitro. Here, we describe the identification of three novel valproic acid derivatives with superior differentiation-inducing and anti-proliferative activities in K562 bcr/abl-positive chronic myeloid leukemia cells and HL60 promyelocytic leukemia cells at achievable therapeutic VPA concentrations. These compounds reveal potent inhibition of histone deacetylase activity, induction of p21Cip/Waf expression as well as low toxicity on CD34+ bone marrow cells.

References

May 1, 1986·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·H Nau, W Löscher
Jan 22, 1998·Anti-cancer Drugs·J CinatlD Schwabe
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·V M RichonP A Marks
Aug 24, 1999·Archives of Pathology & Laboratory Medicine·S J Soldin
Aug 3, 2000·Journal of the National Cancer Institute·P A MarksR A Rifkind
Aug 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·V M RichonP A Marks
Aug 25, 2001·Cancer Letters·O WittA Pekrun
Oct 24, 2001·Current Opinion in Oncology·P A MarksR A Rifkind
Aug 14, 2002·Current Medicinal Chemistry·Roman A BlahetaJindrich Cinatl
Sep 5, 2002·Medicinal Research Reviews·Roman A Blaheta, Jindrich Cinatl
Dec 21, 2002·International Journal of Cancer. Journal International Du Cancer·Yo-ichi YamashitaKeizo Sugimachi
Jan 18, 2003·Blood·Nicholas MitsiadesKenneth C Anderson
Feb 11, 2003·Epilepsy Research·James C CloydUNKNOWN Depacon Study Group
May 29, 2003·Current Cancer Drug Targets·James S ChenRemco A Spanjaard
Feb 12, 2004·Cancer Research·Nadia GurvichPeter S Klein
Jan 8, 2005·Medicinal Research Reviews·Roman A BlahetaJindrich Cinatl

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Citations

Jan 3, 2007·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Meir Bialer, Boris Yagen
Aug 29, 2007·Acta Pharmacologica Sinica·Guo-qiang ChenYun Yu
May 31, 2012·Molekuliarnaia biologiia·D MuthnaM Rezacova
Feb 20, 2009·European Journal of Haematology·Brigitte KircherGünther Gastl
Apr 19, 2015·Biotechnology Advances·Franck MorceauMarc Diederich
Jul 25, 2007·Cancer·Andrea Kuendgen, Norbert Gattermann
Sep 17, 2009·Biochemical Society Transactions·Nicole Terbach, Robin S B Williams
Apr 24, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Till MildeOlaf Witt

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