Abstract
The histone deacetylase (HDAC) enzymes have emerged as an important class of molecular targets in cancer therapy, with five inhibitors in clinical use. Recently, it has been shown that a lack of selectivity between the 11 Zn-dependent HDAC isoforms may lead to unwanted side-effects. In this paper, we show that piano stool Ru complexes can act as HDAC inhibitors, and variation in the capping arene leads to differences in HDAC isoform selectivity.
Keywords:
histone deacetylase inhibitors; ruthenium in medicine; selective enzyme inhibition.
MeSH terms
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Cell Proliferation / drug effects*
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Coordination Complexes / chemistry
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Coordination Complexes / pharmacology
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HeLa Cells
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Histone Deacetylase 1 / antagonists & inhibitors
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Histone Deacetylase 1 / genetics
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Histone Deacetylase 1 / ultrastructure
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Histone Deacetylase 6 / antagonists & inhibitors
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Histone Deacetylase 6 / genetics
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Histone Deacetylase 6 / ultrastructure
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Histone Deacetylase Inhibitors / chemistry
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Histone Deacetylase Inhibitors / pharmacology*
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Humans
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Neoplasms / drug therapy*
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Neoplasms / genetics
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Protein Conformation / drug effects
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Protein Isoforms / genetics
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Ruthenium / chemistry
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Ruthenium / pharmacology
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Ruthenium Compounds / chemistry
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Ruthenium Compounds / pharmacology*
Substances
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Coordination Complexes
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Histone Deacetylase Inhibitors
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Protein Isoforms
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Ruthenium Compounds
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Ruthenium
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HDAC1 protein, human
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HDAC6 protein, human
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Histone Deacetylase 1
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Histone Deacetylase 6