GSK-J4-hydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGSK-J4 hydrochlorideCat. No.: HY-15648FCAS No.: 1797983-09-5分式: CHClNO分量: 453.96作靶點: Histone Demethylase作通路: Epigenetics儲存式: Please store the product under the recommended conditions inthe COA.溶解性數(shù)據(jù)體外實驗 DMSO : 125 mg/mL (275.35

2、mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.2028 mL 11.0142 mL 22.0284 mL5 mM 0.4406 mL 2.2028 mL 4.4057 mL10 mM 0.2203 mL 1.1014 mL 2.2028 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 請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄的儲備液

3、可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (4.58 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (4.58 mM); Clear solutionBIOLOGICAL ACTIVITY物活性GSK-J4 hydrochloride種有效的 H3K27me3/me2

4、 去甲化酶 JMJD3/KDM6B 和 UTX/KDM6A 雙抑制劑，1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEIC50 分別為 8.6 M 和 6.6 M。GSK-J4 hydrochloride 抑制 LPS 誘導(dǎo)的原代巨噬細(xì)胞產(chǎn) TNF-，IC50值為 9 M。GSK-J4 hydrochlorideGSK-J1 的細(xì)胞通透性前藥。IC50 & Target IC50: 8.6 M (JMJD3/KDM6B), 6.6 M (UTX/KDM6A) 6體外研究 GSK-J4 Hydrochloride has cellular act

5、ivity in Flag-JMJD3-transfected HeLa cells, in which GSK-J4 preventsthe JMJD3-induced loss of nuclear H3K27me3 immunostaining. Administration of GSK-J4 increases totalnuclear H3K27me3 levels in untransfected cells. GSK-J4 significantly reduces the expression of 16 of 34LPS-driven cytokines, includin

6、g tumour-necrosis factor- (TNF-) 1.GSK-J4 Hydrochloride (5 M; 48 hours) causes a more than 3-fold increase in mouse podocyte H3K27me3content. H3K27me3 levels in cultured podocytes, GSK-J4 reduces Jagged-1 mRNA and Jagged-1 proteinlevels. Correspondingly, when exposed podocytes to the inducer of dedi

7、fferentiation TGF-1, pretreatmentwith GSK-J4 preventes both the increase in intracellular N1-ICD levels and the increase in -SMA and thedecrease in podocin mRNA levels 2.GSK-J4 Hydrochloride (10, 25 nM) acts upon DCs promoting the differentiation of Treg cells, improving Tregstability and suppressiv

8、e capacities, without affecting the differentiation of Th1 and Th17 cells 3.GSK-J4 Hydrochloride inhibits JMJD3 expression that is induced by TGF-1 4.GSK-J4 Hydrochloride inhibits H3K4 demethylation at Xist, Nodal, and HoxC13 in female embryonic stemcells 5.體內(nèi)研究 GSK-J4 Hydrochloride (10 mg/kg; i.p.;

9、 thrice-weekly for 10 weeks) attenuates the development of kidneydisease in diabetic mice 2.GSK-J4 Hydrochloride (0.5 mg/kg, i.p.) significantly reduces the severity and delays the onset of the diseaseof the mouse model of experimental autoimmune encephalomyelitis 3.Animal Model: Eight-week-old male

10、 db/m and db/db mice on a BKS background 2Dosage: 10 mg/kgAdministration: i.p.; thrice-weekly for 10 weeksResult: Attenuated the development of kidney disease in diabetic mice. 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. 201

11、9 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. 2012Au

12、g 16;488(7411):404-8.2. Majumder S, et al. Shifts in podocyte histone H3K27me3 regulate mouse and human glomerular disease. J Clin Invest. 2018 Jan2;128(1):483-499.3. Donas C, et al. The histone demethylase inhibitor GSK-J4 limits inflammation through the induction of a tolerogenic phenotype on DCs.

13、J Autoimmun. 2016 Dec;75:105-117.4. Yapp C, et al. H3K27me3 demethylases regulate in vitro chondrogenesis and chondrocyte activity in osteoarthritis. Arthritis Res Ther.2016 Jul 7;18(1):1585. Kamikawa YF, et al. Histone demethylation maintains Prdm14 and Tsix expression and represses xIst in embryonic stem cells. PLoSOne. 2015 May 20;10(5):e01256266. Heinemann B, et al. Inhibition of demethylases by GSK-J1/J4. Nature. 2014 Oct 2;514(7520):E1-2