Design and synthesis of a tetrahydroisoquinoline-based hydroxamate derivative (ZYJ-34v), an oral active histone deacetylase inhibitor with potent antitumor activity.

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Zhang Y, Liu C, Chou CJ, Wang X, Jia Y, Xu W

Design and synthesis of a tetrahydroisoquinoline-based hydroxamate derivative (ZYJ-34v), an oral active histone deacetylase inhibitor with potent antitumor activity.

Chem Biol Drug Des. 2013 Aug;82(2):125-30. doi: 10.1111/cbdd.12144. Epub 2013 Jul 1.

PubMed ID
23581848 [ View in PubMed
]
Abstract

In our previous study, we developed a novel series of tetrahydroisoquinoline-based hydroxamic acid derivatives as histone deacetylase inhibitors (Bioorg Med Chem, 2010, 18, 1761-1772; J Med Chem, 2011, 54, 2823-2838), among which, compound ZYJ-34c (1) was identified and validated as the most potent one with marked in vitro and in vivo antitumor potency (J Med Chem, 2011, 54, 5532-5539.). Herein, further modification in 1 afforded another oral active analog ZYJ-34v (2) with simplified structure and lower molecular weight. Biological evaluation of compound 2 showed efficacious inhibition against histone deacetylase 1, 2, 3, and 6, which was confirmed by Western blot analysis results. Most importantly, compound 2 exhibited similar even more potent in vitro and in vivo antitumor activities relative to the approved histone deacetylase inhibitor SAHA.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
VorinostatHistone deacetylase 1IC 50 (nM)75.6N/AN/ADetails
VorinostatHistone deacetylase 2IC 50 (nM)256.4N/AN/ADetails
VorinostatHistone deacetylase 3IC 50 (nM)28.4N/AN/ADetails