Identification of Novel, Selective, and Stable Inhibitors of Class II Histone Deacetylases. Validation Studies of the Inhibition of the Enzymatic Activity of HDAC4 by Small Molecules as a Novel Approa

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• 作者：Jesus M. Ontoria ; Sergio Altamura ; Annalise Di Marco ; Federica Ferrigno ; Ralph Laufer ; Ester Muraglia ; Maria Cecilia Palumbi ; Michael Rowley ; Rita Scarpelli ; Carsten Schultz-Fademrecht ; Sergio Serafin
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：November 12, 2009
• 年：2009
• 卷：52
• 期：21
• 页码：6782-6789
• 全文大小：820K
• 年卷期：v.52,no.21(November 12, 2009)
• ISSN：1520-4804

文摘

5-Aryl-2-(trifluoroacetyl)thiophenes were identified as a new series of class II HDAC inhibitors (HDACi). Further development of this new series led to compounds such as 6h, a potent inhibitor of HDAC4 and HDAC6 (HDAC4 WT IC₅₀ = 310 nM, HDAC6 IC₅₀ = 70 nM) that displays 40-fold selectivity over HDAC1 and improved stability in HCT116 cancer cells (t_1/2 = 11 h). Compounds 6h and 2 show inhibition of α-tubulin deacetylation in HCT116 cells at 1 μM concentration and antiproliferation effects only at concentrations where inhibition of histone H3 deacetylation is observed.