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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Axon ID Name Description From price
2269 AK 1 Potent inhibitor of SIRT with good selectivity for SIRT2 over SIRT1 and SIRT3 €90.00
2270 AK 7 Potent, brain-permeable and selective inhibitor of SIRT2 €90.00
2471 BRD 73954 Dual HDAC 6/8 inhibitor with excellent selectivity over the other HDACs €85.00
2014 CI 994 HDAC inhibitor that causes histone hyperacetylation in living cells €70.00
1645 HDAC6 inhibitor ISOX HDAC6 Inhibitor €105.00
2529 JNJ 26481585 dihydrochloride Potent, orally available second-generation pan-HDAC inhibitor €125.00
1548 LBH 589 HDAC1 Inhibitor €95.00
2430 LW479 HDAC inhibitor with cytotoxicity in a panel of breast cancer cell lines. €135.00
1707 MC 1568 HDAC inhibitor (class IIA selective) €85.00
2505 Mocetinostat Class I selective HDAC inhibitor with broad spectrum antitumor activity €80.00
1803 MS 275 Inhibitor of HDAC (1 and 3 Selective) €80.00
2359 Nexturastat A HDAC6 inhibitor with good selectivity over HDAC1 and HDAC8 €95.00
1853 PCI 34051 HDAC8 Inhibitor €90.00
1801 Pyroxamide HDAC1 Inhibitor €90.00
2195 RGFP 966 HDAC3 specific inhibitor €85.00

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