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

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGivinostatCat. No.: HY-14842CAS No.: 497833-27-9Synonyms: ITF-2357分式: CHNO分量: 421.49作靶点: HDAC作通路: Cell Cycle/DNA Damage; Epigenetics储存式: Please store the product under the recommended conditions inthe COA.BIOLOGICAL ACTIVITY物活性

2、Givinostat (ITF-2357)是HDAC 抑制剂。抑制 HDAC1 和 HDAC3，IC50 分别为 198 nM 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 hHDAC3 hHDAC1 hHDAC11541 nM (IC50) 157 n

3、M (IC50) 198 nM (IC50) 292 nM (IC50)hHDAC6 hHDAC2 hHDAC10 hHDAC7315 nM (IC50) 325 nM (IC50) 340 nM (IC50) 524 nM (IC50)hHDAC5 hHDAC9 hHDAC8 hHDAC4532 nM (IC50) 541 nM (IC50) 854 nM (IC50) 1059 nM (IC50)HD1-B HD1-A HD27.5 nM (IC50) 16 nM (IC50) 10 nM (IC50)体外研究Givinostat (ITF2357) suppresses total LP

4、S-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 (ITF-2357)1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEsuppresses the production of IL-6 in PBMCs stimulated with TLR agonists as well as t

5、he combination of IL-12plus IL-18. IL-6 secretion decreases to 50% at 50 nM Givinostat, but at 100 and 200 nM, there is noreduction 1. As shown by the CCK-8 assay, Givinostat (ITF-2357) inhibits JS-1 cell proliferation in aconcentration-dependent manner. Treatment with Givinostat 500 nM is associate

6、d with significant inhibitionof 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 90%. To achieve a s

7、ignificant 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 (ITF-2357)(1 or 5 mg/kg), there is a 22% reduction for 1 mg/kg and 40% for 5 mg/kg 1.PROTOCOLCell Assay 2 After the JS

8、-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 (ITF-2357) concentrations of 0 nM, 125 nM, 250 nM, 500 nM, and 1000 nM. In the second g

9、roup,Givinostat of relevant concentrations is added concomitantly with 100 nM of LPS solution. Three replicatesare performed for each group. After inoculation at 37C and 5% CO2 for 24 h, each well (100 L) isincubated with 10 L of CCK-8 solution. The plates are incubated at 37C for 1 h and the absorb

10、ance ismeasured at 450 nm using a microplate reader 2.MCE 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 days before use. For the comparison study,Givinostat (ITF23

11、57) at 10 mg/kg is administered orally, and ITF3056 is injected intraperitoneally. One hourafter administration of the compounds, the animals are treated intraperitoneally with LPS from Salmonellatyphimurium at a dose of 2.5 mg/kg. 90 min after the LPS treatment, mice are sacrificed, and sera arecol

12、lected 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 validations on HYPERLINK / www.MedChemEREFERENCES1. Li S, et al. Specifi

13、c 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):8326-39.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE3. Leoni F, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemicinflammation in vivo. Mol Med. 2005 Jan-Dec;11(1-12)