GSK J4 free base

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GSK J4 free base

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

1373423-53-0

包装与价格：

包装	价格(元)
10mg	电议
50mg	电议

产品介绍

GSK J4 free base 是 H3K27me3/me2-去甲基化酶 JMJD3/KDM6B 和 UTX/KDM6A 的有效双重抑制剂，IC50 分别为 8.6 和 6.6 μM。 GSK J4 游离碱抑制 LPS 诱导的 TNF-α；在人原代巨噬细胞中产生，IC50 为 9 μM. GSK J4 是 GSK-J1 的细胞渗透性前药。 GSK J4 free base 诱导内质网应激相关的细胞凋亡。

Cas No.	1373423-53-0
别名	N-[2-(2-吡啶基)-6-(1,2,4,5-四氢-3H-3-苯并氮杂卓-3-基)-4-嘧啶基]-BETA-丙氨酸乙酯
化学名	ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate
Canonical SMILES	CCOC(CCNC1=CC(N2CCC3=CC=CC=C3CC2)=NC(C4=CC=CC=N4)=N1)=O
分子式	C₂₄H₂₇N₅O₂
分子量	417.46
溶解度	<41.75mg/ml in DMSO;<41.75mg/ml in ethanol
储存条件	Store at -20℃
General tips	For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping Condition	Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request
产品描述	GSK-J4 is a potent dual inhibitor of H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A with IC50s of 8.6 and 6.6 μM, respectively. GSK-J4 inhibits LPS-induced TNF-α production in human primary macrophages with an IC50 of 9 μM. GSK J4 is a cell permeable prodrug of GSK-J1[1][2][3]. GSK-J4 has cellular activity in Flag-JMJD3-transfected HeLa cells, in which GSK-J4 prevents the JMJD3-induced loss of nuclear H3K27me3 immunostaining. Administration of GSK-J4 increases total nuclear H3K27me3 levels in untransfected cells. GSK-J4 significantly reduces the expression of 16 of 34 LPS-driven cytokines, including tumour-necrosis factor-α (TNF-α)[1].GSK-J4 (5 μM; 48 hours) causes a more than 3-fold increase in mouse podocyte H3K27me3 content. H3K27me3 levels in cultured podocytes, GSK-J4 reduces Jagged-1 mRNA and Jagged-1 protein levels. Correspondingly, when exposed podocytes to the inducer of dedifferentiation TGF-β1, pretreatment with GSK-J4 preventes both the increase in intracellular N1-ICD levels and the increase in α-SMA and the decrease in podocin mRNA levels[2]. GSK-J4 (10, 25 nM) acts upon DCs promoting the differentiation of Treg cells, improving Treg stability and suppressive capacities, without affecting the differentiation of Th1 and Th17 cells[3].GSK-J4 inhibits JMJD3 expression that is induced by TGF-β1[4].GSK-J4 inhibits H3K4 demethylation at Xist, Nodal, and HoxC13 in female embryonic stem cells[5]. GSK-J4 Hydrochloride (10 mg/kg; i.p.; thrice-weekly for 10 weeks) attenuates the development of kidney disease in diabetic mice[2].GSK-J4 (0.5 mg/kg, i.p.) significantly reduces the severity and delays the onset of the disease of the mouse model of experimental autoimmune encephalomyelitis[3]. References: [1]. Kruidenier L, et al. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature. 2012 Aug 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 Jan 2;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. 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):158 [5]. Kamikawa YF, et al. Histone demethylation maintains Prdm14 and Tsix expression and represses xIst in embryonic stem cells. PLoS One. 2015 May 20;10(5):e0125626 [6]. Heinemann B, et al. Inhibition of demethylases by GSK-J1/J4. Nature. 2014 Oct 2;514(7520):E1-2