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Givinostat (ITF-2357)

Catalog No.GC33050

Givinostat (ITF-2357) (ITF-2357) is a HDAC inhibitor with an IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively.

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Givinostat (ITF-2357) Chemical Structure

Cas No.: 497833-27-9

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2mg
$92.00
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5mg
$138.00
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10mg
$220.00
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50mg
$662.00
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100mg
$1,103.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment:

After the JS-1 cell line is cultured in DMEM with 10% fetal bovine serum for 24 h, 30 wells of JS-1 cells are divided into two groups. In the first group, the culture medium is replaced by complete medium with final Givinostat (ITF-2357) concentrations of 0 nM, 125 nM, 250 nM, 500 nM, and 1000 nM. In the second group, Givinostat of relevant concentrations is added concomitantly with 100 nM of LPS solution. Three replicates are performed for each group. After inoculation at 37°C and 5% CO2 for 24 h, each well (100 μL) is incubated with 10 μL of CCK-8 solution. The plates are incubated at 37°C for 1 h and the absorbance is measured at 450 nm using a microplate reader[2].

Animal experiment:

Mice[1] C57BL/6 mice are housed in the animal facility for at least 5 days before use. For the comparison study, Givinostat (ITF2357) at 10 mg/kg is administered orally, and ITF3056 is injected intraperitoneally. One hour after administration of the compounds, the animals are treated intraperitoneally with LPS from Salmonella typhimurium at a dose of 2.5 mg/kg. 90 min after the LPS treatment, mice are sacrificed, and sera are collected and stored at -80°C until further analysis of cytokine productions.

References:

[1]. Li S, et al. Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo. J Biol Chem. 2015 Jan 23;290(4):2368-78.
[2]. Leoni F, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med. 2005 Jan-Dec;11(1-12):1-15.
[3]. Wang YG, et al. Givinostat inhibition of hepatic stellate cell proliferation and protein acetylation. World J Gastroenterol. 2015 Jul 21;21(27):8326-39.

Background

Givinostat (ITF-2357) is a HDAC inhibitor with an IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively.

Givinostat (ITF2357) suppresses total LPS-induced IL-1β production robustly compared with the reduction by ITF3056. At 25, 50, and 100 nM, Givinostat reduced IL-1β secretion more than 70%. Givinostat (ITF-2357) suppresses the production of IL-6 in PBMCs stimulated with TLR agonists as well as the combination of IL-12 plus IL-18. IL-6 secretion decreases to 50% at 50 nM Givinostat, but at 100 and 200 nM, there is no reduction[1]. As shown by the CCK-8 assay, Givinostat (ITF-2357) inhibits JS-1 cell proliferation in a concentration-dependent manner. Treatment with Givinostat ≥500 nM is associated with significant inhibition of JS-1 cell proliferation (P<0.01). Also, the cell inhibition rate significantly differs between the group cotreated with Givinostat ≥250 nM plus LPS and the group without LPS treatment (same Givinostat concentration) (P<0.05)[2].

Givinostat (ITF2357) at 10 mg/kg is used as a positive control and, as expected, reduced serum TNFα by 60%. Strikingly, pretreatment of ITF3056 starting at 0.1 mg/kg significantly reduces the circulating TNFα by nearly 90%. To achieve a significant increase in serum IL-1β production, a higher dose of LPS is injected (10 mg/kg), and blood is collected after 4 h. Similarly, when pretreated with lower doses of Givinostat (ITF-2357) (1 or 5 mg/kg), there is a 22% reduction for 1 mg/kg and 40% for 5 mg/kg[1].

[1]. Li S, et al. Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo. J Biol Chem. 2015 Jan 23;290(4):2368-78. [2]. Wang YG, et al. Givinostat inhibition of hepatic stellate cell proliferation and protein acetylation. World J Gastroenterol. 2015 Jul 21;21(27):8326-39. [3]. Leoni F, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med. 2005 Jan-Dec;11(1-12):1-15.

Chemical Properties

Cas No. 497833-27-9 SDF
Canonical SMILES O=C(OCC1=CC=C2C=C(CN(CC)CC)C=CC2=C1)NC3=CC=C(C(NO)=O)C=C3
Formula C24H27N3O4 M.Wt 421.49
Solubility Soluble in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.3725 mL 11.8627 mL 23.7254 mL
5 mM 0.4745 mL 2.3725 mL 4.7451 mL
10 mM 0.2373 mL 1.1863 mL 2.3725 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 32 reference(s) in Google Scholar.)

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