Givinostat-hydrochloride-monohydrate-ITF-2357-hydrochloride-monohydrate-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGivinostat hydrochloride monohydrateCat. No.: HY-14842BCAS No.: 732302-99-7Synonyms: ITF-2357 hydrochloride monohydrate分式: CHClNO分量: 475.97作靶点: HDAC作通路: Cell Cycle/DNA Damage; Epigenetics储存式: Powder -20C 3 years4C 2 yearsIn solv

2、ent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (210.10 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.1010 mL 10.5049 mL 21.0097 mL5 mM 0.4202 mL 2.1010 mL 4.2019 mL10 mM 0.2101 mL 1.0505 mL 2.1010 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期

3、限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.17 mg/mL (4.56 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.17 m

4、g/mL (4.56 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.17 mg/mL (4.56 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Givinostat hydrochloride monohydrate (ITF-2357 hydrochloride monohydrate)是HDAC 抑制剂，抑制HDAC1 和 HDAC3，IC50 分别为 198 nM

5、和 157 nM。IC50 & Target hHDAC3 hHDAC1 hHDAC11 hHDAC6157 nM (IC50) 198 nM (IC50) 292 nM (IC50) 315 nM (IC50)hHDAC2 hHDAC10 hHDAC7 hHDAC5325 nM (IC50) 340 nM (IC50) 524 nM (IC50) 532 nM (IC50)hHDAC9 hHDAC8 hHDAC4 HD1-B541 nM (IC50) 854 nM (IC50) 1059 nM (IC50) 7.5 nM (IC50)HD1-A HD216 nM (IC50) 10 nM (

6、IC50)体外研究 Givinostat (ITF2357) suppresses total LPS-induced IL-1 production robustly compared with the reduction byITF3056. At 25, 50, and 100 nM, Givinostat reduced IL-1 secretion more than 70%. Givinostat (ITF2357)suppresses the production of IL-6 in PBMCs stimulated with TLR agonists as well as t

7、he combination of IL-12plus IL-18. IL-6 secretion decreases to 50% at 50 nM Givinostat (ITF2357), but at 100 and 200 nM, there isno reduction 1. As shown by the CCK-8 assay, Givinostat (ITF2357) inhibits JS-1 cell proliferation in aconcentration-dependent manner. Treatment with Givinostat (ITF2357)

8、500 nM is associated with significantinhibition of JS-1 cell proliferation (P 2.体内研究 Givinostat (ITF2357) at 10 mg/kg is used as a positive control and, as expected, reduced serum TNF by60%. Strikingly, pretreatment of ITF3056 starting at 0.1 mg/kg significantly reduces the circulating TNF bynearly

9、90%. To achieve a significant increase in serum IL-1 production, a higher dose of LPS is injected (10mg/kg), and blood is collected after 4 h. Similarly, when pretreated with lower doses of Givinostat (ITF2357)(1 or 5 mg/kg), there is a 22% reduction for 1 mg/kg and 40% for 5 mg/kg 1.PROTOCOLCell As

10、say 2 After the JS-1 cell line is cultured in DMEM with 10% fetal bovine serum for 24 h, 30 wells of JS-1 cells aredivided into two groups. In the first group, the culture medium is replaced by complete medium with finalGivinostat concentrations of 0 nM, 125 nM, 250 nM, 500 nM, and 1000 nM. In the s

11、econd group, Givinostatof relevant concentrations is added concomitantly with 100 nM of LPS solution. Three replicates areperformed for each group. After inoculation at 37C and 5% CO2 for 24 h, each well (100 L) is incubatedwith 10 L of CCK-8 solution. The plates are incubated at 37 C for 1 h and th

12、e absorbance is measured at450 nm using a microplate reader 2.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 C57BL/6 mice are housed in the animal facility for at least 5 da

13、ys before use. For the comparison study,Givinostat (ITF2357) at 10 mg/kg is administered orally, and Givinostat (ITF2357) is injected intraperitoneally.One hour after administration of the compounds, the animals are treated intraperitoneally with LPS fromSalmonella typhimurium at a dose of 2.5 mg/kg

14、. 90 min after the LPS treatment, mice are sacrificed, andsera are collected and stored at -80C until further analysis of cytokine productions.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 J Mol Med (Berl). 2019 Jun 14.See more customer va

15、lidations on HYPERLINK / www.MedChemEREFERENCES1. Li S, et al. Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro andin 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 Jul21;21(27):8326-39.3. Leoni F, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemicinflammation in vivo.