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Givinostat

SKU: orb3027338

Description

Givinostat (ITF-2357) is an orally bioavailable, pan-HDAC inhibitor that blocks STAT5 phosphorylation, demonstrating antitumor effects in crlf2-rearranged BCP-ALL models. Its anti-inflammatory properties, including suppression of TNF-α and IL-1β, and promotion of β-cell survival support research in leukemia, diabetes, and arthritis, as evidenced by in vitro and in vivo studies.
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Research Area

Cell Biology, Epigenetics & Chromatin, Immunology & Inflammation, Molecular Biology, Signal Transduction, Stem Cell & Developmental Biology

Images & Validation

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Givinostat

Key Properties

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CAS Number497833-27-9
MW421.5
Purity98.56%
FormulaC24H27N3O4
SMILESCCN(CC)Cc1ccc2cc(COC(=O)Nc3ccc(cc3)C(=O)NO)ccc2c1
TargetSTAT,IL Receptor,TNF,Apoptosis,HDAC
Solubility10% DMSO+40% PEG300+5% Tween-80+45% Saline:4 mg/mL (9.49 mM);DMSO:160 mg/mL (379.6 mM)

Bioactivity

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Target IC50
HDAC1 (human):198 nM|HD1-A:16 nM|HDAC7 (human):524 nM|HDAC9 (human):541 nM|HDAC11 (human):292 nM|HDAC3 (human):157 nM|HDAC10 (human):340 nM|HDAC6 (human):315 nM|HD1-B:7.5 nM|HD2:10 nM
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In Vivo
Givinostat (ITF2357), used as a positive control at a dose of 10 mg/kg, effectively decreased serum TNFα levels by 60%. Notably, pretreatment with ITF3056, starting at a dosage of 0.1 mg/kg, significantly lowered circulating TNFα levels by up to 90%. To induce a substantial raise in serum IL-1β production, an elevated LPS dose (10 mg/kg) is administered, followed by blood collection after 4 hours. Furthermore, lower doses of Givinostat (ITF-2357) at 1 or 5 mg/kg resulted in a 22% and a 40% reduction in TNFα levels, respectively.
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In Vitro
Givinostat (ITF2357) effectively suppresses IL-1β production induced by LPS, achieving a greater than 70% reduction in IL-1β secretion at concentrations of 25, 50, and 100 nM, outperforming ITF3056. It also inhibits IL-6 production in PBMCs triggered by TLR agonists and the combination of IL-12 plus IL-18, with a 50% decrease in IL-6 secretion at 50 nM, although no further reduction is observed at higher concentrations of 100 and 200 nM. Additionally, Givinostat significantly inhibits JS-1 cell proliferation in a concentration-dependent manner, with concentrations ≥500 nM showing substantial inhibition (P<0.01). Notably, cells co-treated with Givinostat ≥250 nM plus LPS exhibit a significantly higher inhibition rate compared to those treated without LPS at the same Givinostat concentration (P<0.05).
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Cell Research
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.
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Storage & Handling

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Storagestore at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
Expiration Date12 months from date of receipt.
DisclaimerFor research use only

Alternative Names

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ITF-2357, ITF2357, Givinostat

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Quality Guarantee

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Quick Database Links

Gene Symbol
STAT,IL Receptor,TNF,Apoptosis,HDAC

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Givinostat (orb3027338)

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% DMSO +
%+
% Tween 80 +
%

Available Sizes

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1 mg
$ 80.00
1 ml x 10 mM (in DMSO)
$ 120.00
5 mg
$ 120.00
10 mg
$ 180.00
25 mg
$ 330.00
50 mg
$ 510.00
100 mg
$ 740.00
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