Givinostat-hydrochloride-ITF-2357-hydrochloride-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGivinostat hydrochlorideCat. No.: HY-14842ACAS No.: 199657-29-9Synonyms: ITF-2357 hydrochloride分式: CHClNO分量: 457.95作靶點(diǎn): HDAC作通路: Cell Cycle/DNA Damage; Epigenetics儲(chǔ)存式: Please store the product under the recommended conditions in

2、the COA.BIOLOGICAL ACTIVITY物活性 Givinostat hydrochloride (ITF-2357 hydrochloride)是HDAC 抑制劑，抑制 HDAC1 和 HDAC3，IC50 分別為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) 53

3、2 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 (IC50)體外研究 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 secreti

4、on more than 70%. Givinostat (ITF-2357)suppresses the production of IL-6 in PBMCs stimulated with TLR agonists as well as the 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 (I

5、TF-2357) inhibits JS-1 cell proliferation in aconcentration-dependent manner. Treatment with Givinostat (ITF-2357) 500 nM is associated withsignificant inhibition of JS-1 cell proliferation (P 2.1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體內(nèi)研究 Givinostat (ITF2357) at 10 mg/kg is used as a posit

6、ive control and, as expected, reduced serum TNF by60%. Strikingly, pretreatment of Givinostat (ITF-2357) starting at 0.1 mg/kg significantly reduces thecirculating TNF by nearly 90%. To achieve a significant increase in serum IL-1 production, a higher dose ofLPS is injected (10 mg/kg), and blood is

7、collected after 4 h. Similarly, when pretreated with lower doses ofITF3056 (1 or 5 mg/kg), there is a 22% reduction for 1 mg/kg and 40% for 5 mg/kg 1.PROTOCOLKinase Assay 1 Recombinant human HDAC enzymes (HDAC1- HDAC11) are used. Activity of HDAC1, HDAC2, HDAC3,HDAC6, HDAC10 and HDAC11 is assayed us

8、ing the Fluor de Lys deacetylase substrate. HDAC8 activity isassayed using Fluor de Lys Green deacetylase substrate. N-Trifluoroacetyl-L-lysine is used to assay activityof HDAC4, HDAC5, HDAC7 and HDAC9. Recombinant enzymes are preincubated with Givinostat (ITF2357)or ITF3056 at 30C in a volume of 25

9、 L in wells of a microtiter plate. After a brief incubation, 25 L ofsubstrate is added, and the fluorescent signal is generated by the addition of 50 L of developer containing 2M Trichostatin A. For each assay, the amount of enzyme, incubation times, assay buffer, and concentrationof the substrates

10、are optimized. Positive control for enzyme activity consisted of enzyme plus substratewithout Givinostat or ITF3056. The fluorescence signal is detected using a Victor multilabel plate reader 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay

11、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 secon

12、d group, Givinostat(ITF-2357) 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 37 C for 1 h

13、 and the absorbance 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,Gi

14、vinostat (ITF2357) at 10 mg/kg is administered orally, and Givinostat (ITF-2357) is injectedintraperitoneally. One hour after administration of the compounds, the animals are treated intraperitoneallywith LPS from Salmonella typhimurium at a dose of 2.5 mg/kg. 90 min after the LPS treatment, mice ar

15、esacrificed, and sera 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.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) J Mol Med (Berl). 2019 Jun 14.See more customer validations on HYPERLINK / www.MedChemEREFE

16、RENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. 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 systemicinfla