Deacetylase

Deacetylase

Histone deacetylases (HDACs; EC 3.5.1.98) are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid of histones. Inhibitors of this class of enzymes have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics. Moreover, Histone deacetylase inhibitors (HDIs) are being studied as an alleviator or treatment for neurodegenerative diseases. Recently, this class of enzymes is emerging as an exciting new class of potential anticancer agents for the treatment of solid and hematological malignancies by inhibiting the proliferation and induction of differentiation and/or apoptosis of tumor cells in culture and in animal models. HDAC inhibition causes acetylated nuclear histones to accumulate in both tumor and normal tissues, providing a surrogate marker for the biological activity of HDAC inhibitors in vivo. HDAC inhibition not only results in acetylation of histones but also transcription factors such as p53, GATA-1 and estrogen receptor-alpha. The functional significance of acetylation of non-histone proteins and the precise mechanisms whereby HDAC inhibitors induce tumor cell growth arrest, differentiation and/or apoptosis are currently the focus of intensive research. Several HDAC inhibitors have shown impressive antitumor activity in vivo with remarkably little toxicity in preclinical studies.Besides HDACs, multiple sirtuins (NAD+-dependent deacetylase sirtuin, SIRT; EC 3.5.1.98) are known to show deacetylase activity. They are considered class III histone deacetylases that deacetylate histones and transcription factors. In turn, sirtuins can be inhibited by nicotinamide, which binds to a specific receptor site of the enzyme, so it is thought that drugs that interfere with this binding should increase sirtuin activity. Development of new agents that would specifically block the nicotinamide-binding site could provide an avenue for development of newer agents to treat degenerative diseases such as cancer, Alzheimer\'s, diabetes, atherosclerosis, and gout.SIRT1 is involved in other signaling pathways as well, since it competes with HDAC1 in deacetylation of PTEN, an important phosphatase involved in cell signaling via phosphoinositols and the PI3K/AKT/mTOR signaling pathway. Aiming to keep up with these recent developments in oncology research,Axon Medchem recently added a significant number of HDAC inhibitors to its ever broadening range of products.

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    1548
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    1645
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    1707
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    1777
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    1801
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    1803
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  • PCI 34051
    1853
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  • SRT 1720 tetrahydrochloride
    1875
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  • Selisistat
    1956
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  • Tubastatin A hydrochloride
    2004
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  • Tenovin 1
    2008
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    From $77.00

  • CI 994
    2014
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  • TMP 195
    2180
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  • RGFP 966
    2195
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    2209
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More About Deacetylase

Histone deacetylases (HDACs; EC 3.5.1.98) are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid of histones. Inhibitors of this class of enzymes have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics. Moreover, Histone deacetylase inhibitors (HDIs) are being studied as an alleviator or treatment for neurodegenerative diseases[1]. Recently, this class of enzymes is emerging as an exciting new class of potential anticancer agents for the treatment of solid and hematological malignancies[2] by inhibiting the proliferation and induction of differentiation and/or apoptosis of tumor cells in culture and in animal models[3]. HDAC inhibition causes acetylated nuclear histones to accumulate in both tumor and normal tissues, providing a surrogate marker for the biological activity of HDAC inhibitors in vivo[4]. HDAC inhibition not only results in acetylation of histones but also transcription factors such as p53, GATA-1 and estrogen receptor-alpha. The functional significance of acetylation of non-histone proteins and the precise mechanisms whereby HDAC inhibitors induce tumor cell growth arrest, differentiation and/or apoptosis are currently the focus of intensive research. Several HDAC inhibitors have shown impressive antitumor activity in vivo with remarkably little toxicity in preclinical studies.
Besides HDACs, multiple sirtuins (NAD+-dependent deacetylase sirtuin, SIRT; EC 3.5.1.98) are known to show deacetylase activity. They are considered class III histone deacetylases that deacetylate histones and transcription factors[5]. In turn, sirtuins can be inhibited by nicotinamide, which binds to a specific receptor site of the enzyme, so it is thought that drugs that interfere with this binding should increase sirtuin activity. Development of new agents that would specifically block the nicotinamide-binding site could provide an avenue for development of newer agents to treat degenerative diseases such as cancer, Alzheimer's, diabetes, atherosclerosis, and gout[6].
SIRT1 is involved in other signaling pathways as well, since it competes with HDAC1 in deacetylation of PTEN, an important phosphatase involved in cell signaling via phosphoinositols and the PI3K/AKT/mTOR signaling pathway. Aiming to keep up with these recent developments in oncology research,Axon Medchem recently added a significant number of HDAC inhibitors to its ever broadening range of products.


[1] Histone deacetylase inhibitors: possible implications for neurodegenerative disorders. E. Hahnenet al. Expert Opin Investig Drugs. 2008, 17, 169-84.
[2] The Histone Deacetylase Inhibitor LBH589 Is a Potent Antimyeloma Agent that Overcomes Drug Resistance. Maiso P. et al. Cancer Res 2006, 66, 5781.
[3] Use of the Nitrile Oxide Cycloaddition (NOC) Reaction for Molecular Probe Generation: A New Class of Enzyme Selective Histone Deacetylase Inhibitors (HDACIs) Showing Picomolar Activity at HDAC6. AP Kozikowski et al.  J. Med. Chem. 2008, 51, 4370–4373.
[4] Histone deacetylase inhibitors in cancer treatment. Vigushin DM, Coombes RC. Anticancer Drugs. 2002 ,13, 1-13.
[5] Histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear translocation. S. Hisahara et al. PNAS 2008, 105, 15599-15604.
[6] Sirtuin activators. F.J. Alcaín, J.M. Villalba. Exp. Opin. Ther. Pat. 2009, 19, 403-414.

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