Size | Price | Stock | Qty |
---|---|---|---|
1mg |
|
||
2mg |
|
||
5mg |
|
||
10mg |
|
||
25mg |
|
||
50mg |
|
||
100mg |
|
||
250mg |
|
||
Other Sizes |
|
Purity: ≥98%
Givinostat (formerly ITF2357; Gavinostat) is a potent and orally bioavailable inhibitor of both class I and class II histone deacetylase (HDAC) with potential anticancer activity. It inhibits HDAC with IC50 values for HDAC1 and HDAC3 of 198 and 157 nM, respectively.In vitro, JAKEV617F-bearing progenitor cells from chronic myeloproliferative neoplasms efficiently inhibit the formation of hematopoietic colonies by glinostat.
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 )
|
|
---|---|---|
ln Vitro |
|
|
ln Vivo |
|
|
Enzyme Assay |
The procedure for the assay involves mixing the crude cellular extract (5 μL) with 100 μL substrate (2×105 cpm), 40 μL buffer (50 mM Tris-HCl, pH 8.0, 750 mM NaCl, 5 mM PMSF, 50% glycerol), and 95 μL distilled water. To check for HDAC inhibition, add 50 μL of ITF2357. After the mixture has been incubated for a full night at room temperature, 50 μL of a solution made of 259 μL 37% HCl, 28 μL acetic acid, and 1 mL distilled water is added to quench the reaction. The organic extraction method is used to separate the [3H]acetyl residues that are released from the substrate. A beta-counter is used to measure radioactivity after adding 200 μL of the organic phase to standard scintillation fluid. By measuring the difference between the radioactivity of the inhibitor-containing samples and the control sample that only contained cellular crude extract, one can determine the concentration of HDACs that inhibits 50% of the control activity.
|
|
Cell Assay |
The isolated PBMCs are cleaned, then resuspended at 5×106/mL in RPMI with 5% FCS, transferred to a 50-mL conical polypropylene tube, and kept at 4 °C for the night. A 96-well flat microtiter plate is filled with 100 μL of PBMCs after they have been resuspended the previous morning. The plates are then incubated at 37 °C for an hour after adding ITF2357 for the inhibition studies. The cells are then stimulated with LPS or other stimulants in a final volume of 200 μL per well. After being incubated for 24 hours at 37 °C, the supernatants are removed and frozen at -80 °C until they are tested for cytokines.
|
|
Animal Protocol |
|
|
References |
Molecular Formula |
C24H27N3O4.HCL.H2O
|
|
---|---|---|
Molecular Weight |
475.97
|
|
Exact Mass |
475.19
|
|
Elemental Analysis |
C, 60.56; H, 6.35; Cl, 7.45; N, 8.83; O, 16.81
|
|
CAS # |
732302-99-7
|
|
Related CAS # |
|
|
Appearance |
White to beige solid powder
|
|
SMILES |
CCN(CC)CC1=CC2=C(C=C1)C=C(C=C2)COC(=O)NC3=CC=C(C=C3)C(=O)NO.O.Cl
|
|
InChi Key |
FKGKZBBDJSKCIS-UHFFFAOYSA-N
|
|
InChi Code |
InChI=1S/C24H27N3O4.ClH.H2O/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;1H2
|
|
Chemical Name |
[6-(diethylaminomethyl)naphthalen-2-yl]methyl N-[4-(hydroxycarbamoyl)phenyl]carbamate;hydrate;hydrochloride
|
|
Synonyms |
ITF 2357; ITF2357; ITF-2357; Givinostat; gavinostat; ITF2357 HCl; ITF2357 hydrochloride; Givinostat HCl
|
|
HS Tariff Code |
2934.99.9001
|
|
Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
|
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
Solubility (In Vitro) |
|
|||
---|---|---|---|---|
Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (4.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.17 mg/mL (4.56 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.17 mg/mL (4.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 30% propylene glycol, 5% Tween 80, 65% D5W: 30mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.1010 mL | 10.5049 mL | 21.0097 mL | |
5 mM | 0.4202 mL | 2.1010 mL | 4.2019 mL | |
10 mM | 0.2101 mL | 1.0505 mL | 2.1010 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.
td> |
Effects of oral ITF2357 on STZ-induced β-cell toxicity, serum nitric oxide levels and spleen cell responses in vivo.Mol Med.2011May-Jun;17(5-6):369-77. td> |
Effect of HDAC inhibition on cytokine-induced INS-1 cell death.Mol Med.2011May-Jun;17(5-6):369-77. td> |
ITF2357 protects from cytokine-induced islet injury in vitro.Mol Med.2011May-Jun;17(5-6):369-77. td> |