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Chemical Structure| 497833-27-9 Chemical Structure| 497833-27-9

Structure of Givinostat
CAS No.: 497833-27-9

Chemical Structure| 497833-27-9

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Givinostat is a potent HDAC inhibitor for Maize HD2, HD1-B and HD1-A with IC50 of 10 nM, 7.5 nM and 16 nM,respectively.

Synonyms: ITF-2357; Duvyzat

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Huang, He-Ming ; Zhou, Xiao-Ru ; Liu, Yan-Jun ; Fan, Shi-Jie ; Liao, Li-Ping ; Huang, Jing , et al.

Abstract: Hepatic fibrosis, a common pathological manifestation of chronic liver injury, is generally considered to be the end result of an increase in extracellular matrix produced by activated hepatic stellate cells (HSCs). The aim of the present study was to target the mechanisms underlying HSC activation in order to provide a powerful therapeutic strategy for the prevention and treatment of liver fibrosis. In the present study, a high-throughput screening assay was established, and the histone deacetylase inhibitor givinostat was identified as a potent inhibitor of HSC activation in vitro. Givinostat significantly inhibited HSC activation in vivo, ameliorated carbon tetrachloride-induced mouse liver fibrosis and lowered plasma aminotransferases. Transcriptomic analysis revealed the most significantly regulated genes in the givinostat treatment group in comparison with those in the solvent group, among which, dermokine (Dmkn), mesothelin (Msln) and uroplakin-3b (Upk3b) were identified as potential regulators of HSC activation. Givinostat significantly reduced the mRNA expression of Dmkn, Msln and Upk3b in both a mouse liver fibrosis model and in HSC-LX2 cells. Knockdown of any of the aforementioned genes inhibited the TGF-β1-induced expression of α-smooth muscle actin and collagen type I, indicating that they are crucial for HSC activation. In summary, using a novel strategy targeting HSC activation, the present study identified a potential epigenetic drug for the treatment of hepatic fibrosis and revealed novel regulators of HSC activation.

Keywords: liver fibrosis ; hepatic stellate cell ; histone deacetylase inhibitor ; epigenetics ; givinostat

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Product Details of Givinostat

CAS No. :497833-27-9
Formula : C24H27N3O4
M.W : 421.49
SMILES Code : O=C(OCC1=CC=C2C=C(CN(CC)CC)C=CC2=C1)NC3=CC=C(C(NO)=O)C=C3
Synonyms :
ITF-2357; Duvyzat
English Name :(6-((Diethylamino)methyl)naphthalen-2-yl)methyl (4-(hydroxycarbamoyl)phenyl)carbamate
MDL No. :MFCD16619317

Safety of Givinostat

Related Pathways of Givinostat

epigenetics
JAK-STAT

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Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.37mL

0.47mL

0.24mL

11.86mL

2.37mL

1.19mL

23.73mL

4.75mL

2.37mL

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