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

Item Type:	Article
Title:	Novel valproic acid derivatives with potent differentiation-inducing activity in myeloid leukemia cells
Creators Name:	Deubzer, H. and Busche, B. and Rönndahl, G. and Eikel, D. and Michaelis, M. and Cinatl, J. and Schulze, S. and Nau, H. and Witt, O.
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 p21(Cip/Waf) expression as well as low toxicity on CD34(+) bone marrow cells.
Keywords:	VPA, Differentiation, HDAC, Leukemia, K562, HL60, p21(Cip/Waf)
Source:	Leukemia Research
ISSN:	0145-2126
Publisher:	Elsevier / Pergamon
Volume:	30
Number:	9
Page Range:	1167-1175
Date:	September 2006
Official Publication:	https://doi.org/10.1016/j.leukres.2006.01.009
PubMed:	View item in PubMed

Repository Staff Only: item control page