Histone deacetylase (HDAC) inhibitors offer a promising strategy for cancer therapy and the first generation HDAC inhibitors are currently in clinical trials. A structurally novel series of HDAC inhibitors based on the natural cyclic tetrapeptide Apicidin is described. Selected screening of the sample collection looking for L-2-amino-8-oxodecanoic acid (L-Aoda) derivatives identified a small acyclic lead molecule 1 with the unusual ketone zinc binding group. SAR studies around this lead resulted in optimization to potent, low molecular weight, selective, non-hydroxamic acid HDAC inhibitors, equipotent to current clinical candidates.
A series of novel, potent, and selective histone deacetylase inhibitors / P. Jones, S. Altamura, P.K. Chakravarty, O. Cecchetti, R.D. Francesco, P. Gallinari, R. Ingenito, P.T. Meinke, A. Petrocchi, M. Rowley, R. Scarpelli, S. Serafini, C. Steinkühler. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 16:23(2006), pp. 5948-5952. [10.1016/j.bmcl.2006.09.002]
A series of novel, potent, and selective histone deacetylase inhibitors
R.D. Francesco;
2006
Abstract
Histone deacetylase (HDAC) inhibitors offer a promising strategy for cancer therapy and the first generation HDAC inhibitors are currently in clinical trials. A structurally novel series of HDAC inhibitors based on the natural cyclic tetrapeptide Apicidin is described. Selected screening of the sample collection looking for L-2-amino-8-oxodecanoic acid (L-Aoda) derivatives identified a small acyclic lead molecule 1 with the unusual ketone zinc binding group. SAR studies around this lead resulted in optimization to potent, low molecular weight, selective, non-hydroxamic acid HDAC inhibitors, equipotent to current clinical candidates.File | Dimensione | Formato | |
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