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Givinostat hydrochloride monohydrate  ≥98%

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包装规格：5mg 10mg 25mg 50mg in glass bottle
溶解性：溶于DMSO（≥100mg/mL）
产品描述：基本信息 产品编号：G10403 产品名称：Givinostat hydrochloride monohydrate CAS: 732302-99-7   储存条件 粉末 -20℃ 四年     分子式： C24H27N3O4.HCl.H2O 溶于液体 -80℃ 六个月 分子量 475.97 -20℃ 一个月 化学名：  [6-(diethylaminomethyl)naphthalen-2-yl]methyl N-[4-(hydroxycarbamoyl)phenyl]carbamate;hydrate;hydrochloride   Solubility (25°C)   体外 DMSO ≥100mg/mL (210.10mM) Ethanol   Water   体内 现配现用   ＜1mg/ml表示微溶或不溶。 普西唐提供的所有化合物浓度为内部测试所得，实际溶液度可能与公布值有所偏差，属于正常的批间细微差异现象。 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；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。   制备储备液   浓度   溶液体积 质量   1mg   5mg   10mg 1mM 2.1010mL 10.5049mL 21.0097mL 5mM 0.4202mL 2.1010mL 4.2019mL 10mM 0.2101mL 1.0505mL 2.1010mL   生物活性 产品描述 一种HDAC 抑制剂，抑制 HDAC1 和 HDAC3，IC50 分别为 198nM 和 157nM。 靶点/IC50 hHDAC3 157nM (IC50) hHDAC1 198nM (IC50) hHDAC11 292nM (IC50) hHDAC6 315nM (IC50) hHDAC2 325nM (IC50) hHDAC10 340nM (IC50) hHDAC7 524nM (IC50) hHDAC5 532nM (IC50） hHDAC9 541nM (IC50) hHDAC8 854nM (IC50) hHDAC4 1059nM (IC50) HD1-B 7.5nM (IC50) HD1-A 16nM (IC50) HD2 10nM (IC50)     体外研究 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 (ITF2357) 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 50nM Givinostat (ITF2357), but at 100 and 200nM, there is no reduction[1]. As shown by the CCK-8 assay, Givinostat (ITF2357) inhibits JS-1 cell proliferation in a concentration-dependent manner. Treatment with Givinostat (ITF2357) ≥500nM 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 ≥250nM plus LPS and the group without LPS treatment (same Givinostat concentration) (P<0.05).   体内研究 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 4h. Similarly, when pretreated with lower doses of Givinostat (ITF2357) (1 or 5 mg/kg), there is a 22% reduction for 1mg/kg and 40% for 5mg/kg.   推荐实验方法(仅供参考) 细胞实验： Cell Assay 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 concentrations of 0nM,125nM, 250nM, 500nM, and 1000nM. In the second group, Givinostat of relevant concentrations is added concomitantly with 100nM of LPS solution. Three replicates are performed for each group. After inoculation at 37°C and 5% CO2 for 24 h,each well (100μL) is incubated with 10μL of CCK-8 solution. The plates are incubated at 37 °C for 1 h and the absorbance is measured at 450nm using a microplate reader.   动物实验:   Animal Administration Mice 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 Givinostat (ITF2357) 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. 90min after the LPS treatment, mice are sacrificed, and sera are collected and stored at -80°C until further analysis of cytokine productions.
保存条件：-20℃

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