GSK-J4-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGSK-J4Cat. No.: HY-15648BCAS No.: 1373423-53-0分式: CHNO分量: 417.5作靶點: Histone Demethylase作通路: Epigenetics儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 36 mg/mL (86.23 mM)* means soluble, bu

2、t saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.3952 mL 11.9760 mL 23.9521 mL5 mM 0.4790 mL 2.3952 mL 4.7904 mL10 mM 0.2395 mL 1.1976 mL 2.3952 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗 GSK-J4 is prepared in 0.1% DMSO in PBS6.BIOLOGICAL ACTIVITY物活性 GSK-J4種有效的H3K27m

3、e3組蛋賴氨酸脫甲基酶 (KDM) 抑制劑，抑制 KDM6B和KDM6A的 IC50 分別為8.6 M 和 6.6 M。IC50 & Target IC50: 8.6 M (KDM6B), 6.6 M (KDM6A) 51/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 GSK-J4 has cellular activity in Flag-JMJD3-transfected HeLa cells, in which GSK-J4 prevents the JMJD3-induced loss of nuclear H3K27me3 i

4、mmunostaining. Administration of GSK-J4 increases total nuclearH3K27me3 levels in untransfected cells. GSK-J4 significantly reduces the expression of 16 of 34 LPS-drivencytokines, including tumour-necrosis factor- (TNF-) 1. GSK-J4 (10, 25 nM) acts upon DCs promoting thedifferentiation of Treg cells,

5、 improving Treg stability and suppressive capacities, without affecting thedifferentiation of Th1 and Th17 cells 2. GSK-J4 inhibits the KDM6 family of H3K27me3 demethylasesJMJD3 and UTX. GSK-J4 inhibits JMJD3 expression that is induced by TGF-1 3. GSK-J4 inhibits H3K4demethylation at Xist, Nodal, an

6、d HoxC13 in female embryonic stem cells 4.體內(nèi)研究 GSK-J4 (0.5 mg/kg, i.p.) significantly reduces the severity and delays the onset of the disease of the mousemodel of experimental autoimmune encephalomyelitis 2.PROTOCOLAnimal Six-to eight-week-old female C57BL/6 WT mice are injected by subcutaneous inj

7、ection (s.c.) with 50 gAdministration 2 myelin oligodendrocyte glycoprotein 35-55 peptide (pMOG) emulsified in Complete Freunds Adjuvant (CFA)supplemented with heat-inactivated Mycobacterium tuberculosis H37 RA. In addition, mice receiveintraperitoneal injection (i.p.) of 500 ng of pertussis toxin o

8、n days 0 and 2. Clinical signs are assessed dailyaccording to the following scoring criteria: 0, no detectable signs; 1, flaccid tail; 2, hind limb weakness orabnormal gait; 3, complete hind limb paralysis; 4, paralysis of fore and hind limbs; and 5, moribund or death.A stock solution of GSK-J4 of 4

9、2 mg/mL (100 mM) is prepared in dimethyl sulfoxide (DMSO) to preservestability. Before injection, the stock solution is diluted 1/10 with ethanol (DMSO: ethanol, 1:10 v/v) andbrought to a final concentration of 140 g/mL in PBS. In systemic drug evaluation experiments, each mousereceive daily i.p. in

10、jections (from days 0-5) of 100 L of this solution containing 14.0 g of the GSK-J4(equivalent to 0.56 mg/kg of the drug). Control mice receive 100 L of the vehicle during the same period. Inother EAE experiments, 106 bone marrow-derived DCs from WT mice are treated with GSK-J4 or vehiclealone for 16

11、 h, pulsed with 5 g/mL of pMOG for 4 h and then transferred i.v. into WT C57BL/6 recipient mice14 and 7 days before EAE induction. In other adoptive transfer EAE experiments, CD4+Foxp3+ Treg cellsgenerated in the presence or absence of 25 nM GSK-J4 are purified by cell sorting and then0.75106 transf

12、erred i.v. into WT C57BL/6 recipient mice 1 day before EAE induction.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 J Clin Invest. 2018 Jan 2;128(1):483-499. Biochem J. 2019 Jun 26;476(12):1741-1751. IUBMB Life. 2019 Jun 26. Oncol Rep. 2019

13、 May;41(5):2667-2678. Patent. US20180263995A1.See more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Kruidenier L, et al. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature. 2012Aug

14、 16;488(7411):404-8.2. Donas C, et al. The histone demethylase inhibitor GSK-J4 limits inflammation through the induction of a tolerogenic phenotype on DCs.J Autoimmun. 2016 Dec;75:105-117.3. Yapp C, et al. H3K27me3 demethylases regulate in vitro chondrogenesis and chondrocyte activity in osteoarthr

15、itis. Arthritis Res Ther.2016 Jul 7;18(1):1584. Kamikawa YF, et al. Histone demethylation maintains Prdm14 and Tsix expression and represses xIst in embryonic stem cells. PLoSOne. 2015 May 20;10(5):e01256265. Heinemann B, et al. Inhibition of demethylases by GSK-J1/J4. Nature. 2014 Oct 2;514(7520):E1-26. Majumder S, et al. Shifts in podocyte histone H3K27me3 regulate mouse and human glomerular disease. J Clin Inv