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J Med Chem. 2009 Nov 12;52(21):6782-9. doi: 10.1021/jm900555u.

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 approach for cancer therapy.

Author information

1
Istituto Di Ricerche Di Biologia Molecolare, P. Angeletti SpA (IRBM-MRL, Rome), Via Pontina Km 30,600, I-00040 Pomezia, Italy. jmontoria@gmail.com

Abstract

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 IC(50) = 310 nM, HDAC6 IC(50) = 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 alpha-tubulin deacetylation in HCT116 cells at 1 microM concentration and antiproliferation effects only at concentrations where inhibition of histone H3 deacetylation is observed.

PMID:
19888759
DOI:
10.1021/jm900555u
[Indexed for MEDLINE]

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