| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
Givinostat (ITF-2357 hydrochloride) is a potent and orally bioactive HDAC inhibitor with potential anti-inflammatory, anti-angiogenic, and anticancer activities. Moreover, a strong inhibitor of the in vitro formation of hematopoietic colonies by progenitor cells bearing JAKEV617F from chronic myeloproliferative neoplasms. Following p21 induction and Bcl-2 and Mcl-1 protein down-modulation, ITF2357 causes apoptosis in multiple myeloma (MM) and acute myelogenous leukemia (AML) cells. It also prevents peripheral blood mononuclear cells from producing pro-inflammatory cytokines.
| Targets |
hHDAC3 (IC50 = 157 nM); hHDAC1 (IC50 = 198 nM); hHDAC11 (IC50 = 292 nM); hHDAC6 (IC50 = 315 nM); hHDAC2 (IC50 = 325 nM); hHDAC10 (IC50 = 340 nM); hHDAC7 (IC50 = 524 nM); hHDAC5 (IC50 = 532 nM); hHDAC9 (IC50 = 541 nM); hHDAC8 (IC50 = 854 nM); hHDAC4 (IC50 = 1059 nM); HD1-B (IC50 = 7.5 nM); HD1-A (IC50 = 16 nM); HD2 (IC50 = 10 nM)
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| ln Vitro |
Givinostat (ITF2357) effectively inhibits the production of IL-1β induced by LPS in its entirety, as opposed to ITF3056's reduction. Givinostat inhibits IL-1β secretion by over 70% at concentrations of 25, 50, and 100 nM. When TLR agonists or the combination of IL-12 and IL-18 are used to stimulate PBMCs, glinotanost inhibits the production of IL-6. Givinostat at 50 nM causes IL-6 secretion to drop to 50%, but at 100 and 200 nM, there is no reduction[1]. Using the CCK-8 assay, ginostat (ITF-2357) inhibits the growth of JS-1 cells in a concentration-dependent manner. Proliferation of JS-1 cells is significantly inhibited when treated with Givinostat (ITF-2357) at concentrations ≥500 nM. There is a significant difference in the cell inhibition rate between the group that received LPS treatment without any treatment and the group that received Givinostat (ITF-2357) ≥250 nM in addition[2].
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| ln Vivo |
Givinostat (ITF2357), a positive control, lowers serum TNFα by 60% when administered at a dose of 10 mg/kg. TNFα in circulation is markedly decreased by almost 90% with pretreatment with Givinostat (ITF-2357), starting at 0.1 mg/kg. A larger dose of LPS (10 mg/kg) is injected, and blood is taken after 4 hours to obtain a notable increase in serum IL-1β production[1].
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| Enzyme Assay |
The enzymes HDAC1–HDAC11 are recombinant human HDACs. Assays for HDAC1, HDAC2, HDAC3, HDAC6, HDAC10, and HDAC11 activity are conducted using the Fluor de Lys deacetylase substrate. With Fluor de Lys Green deacetylase substrate, HDAC8 activity is measured. Assays for HDAC4, HDAC5, HDAC7, and HDAC9 are performed using N-trifluoroacetyl-L-lysine. Pre-incubation of recombinant enzymes is carried out in microtiter plate wells using 25 μL of Givinostat (ITF2357) or ITF3056 at 30°C. 25 μL of substrate is added after a brief incubation period, and 50 μL of developer containing 2 μM Trichostatin A is added to produce the fluorescent signal. The concentration of the substrates, assay buffer, incubation times, and enzyme quantity are all optimized for each assay. Enzyme plus substrate was used as a positive control for enzyme activity in the absence of ITF3056 or Givinostat. The Victor multilabel plate reader is used to find the fluorescence signal[1].
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| Cell Assay |
Following a 24-hour culture period in DMEM supplemented with 10% fetal bovine serum, 30 wells containing JS-1 cells are split into two groups. Complete medium with final Givinostat concentrations of 0 nM, 125 nM, 250 nM, 500 nM, and 1000 nM is used in place of the culture medium in the first group. In the second group, 100 nM of LPS solution is added concurrently with Givinostat (ITF-2357) at appropriate concentrations. For every group, three replicates are carried out. Following a 24-hour inoculation period at 37°C and 5% CO2, 10 μL of CCK-8 solution is incubated in each well (100 μL). A microplate reader is used to measure the absorbance at 450 nm after the plates are incubated for one hour at 37 °C[2].
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| Animal Protocol |
Mice: For a minimum of five days prior to usage, C57BL/6 mice are kept in the animal facility. Givinostat (ITF2357) is injected intraperitoneally and given orally at a dose of 10 mg/kg for the purposes of the comparison study. LPS from Salmonella typhimurium is administered intraperitoneally to the animals at a dose of 2.5 mg/kg one hour after the compounds are administered. Serum is collected and kept at -80°C until further examination of cytokine production, and mice are sacrificed 90 minutes after the LPS treatment.
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| References |
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| Molecular Formula |
C24H27N3O4.HCL
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| Molecular Weight |
457.96
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| Exact Mass |
457.1768341
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| Elemental Analysis |
C, 62.95; H, 6.16; Cl, 7.74; N, 9.18; O, 13.97
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| CAS # |
199657-29-9
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| Related CAS # |
Givinostat;497833-27-9;Givinostat hydrochloride monohydrate;732302-99-7
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| Appearance |
Solid powder
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| SMILES |
CCN(CC)CC1=CC2=C(C=C1)C=C(C=C2)COC(=O)NC3=CC=C(C=C3)C(=O)NO.Cl
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| InChi Key |
QKSGNWJOQMSBEP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H27N3O4.ClH/c1-3-27(4-2)15-17-5-7-21-14-18(6-8-20(21)13-17)16-31-24(29)25-22-11-9-19(10-12-22)23(28)26-30;/h5-14,30H,3-4,15-16H2,1-2H3,(H,25,29)(H,26,28);1H
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| Chemical Name |
[6-(diethylaminomethyl)naphthalen-2-yl]methyl N-[4-(hydroxycarbamoyl)phenyl]carbamate;hydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1836 mL | 10.9180 mL | 21.8360 mL | |
| 5 mM | 0.4367 mL | 2.1836 mL | 4.3672 mL | |
| 10 mM | 0.2184 mL | 1.0918 mL | 2.1836 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01761968 | Active Recruiting |
Drug: givinostat | Chronic Myeloproliferative Neoplasms |
Italfarmaco | March 2013 | Phase 2 |
| NCT05933057 | Not yet recruiting | Drug: Givinostat Drug: Placebo |
Duchenne Muscular Dystrophy | Italfarmaco | December 2023 | Phase 3 |
| NCT06093672 | Not yet recruiting | Drug: Givinostat Hydrochloride Drug: Hydroxy Urea |
Polycythemia Vera | Italfarmaco | December 2023 | Phase 3 |
| NCT05860114 | Completed | Drug: Givinostat | Drug Drug Interaction | Italfarmaco | March 21, 2022 | Phase 1 |
| NCT05845567 | Completed | Drug: Givinostat Drug: Clarithromycin |
Drug Drug Interaction | Italfarmaco | March 21, 2022 | Phase 1 |
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