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GSK J4 HCl

现货
Catalog No.
A4190
H3K27去甲基化酶JMJD3的抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,320.00
现货
10mg
¥ 1,100.00
现货
50mg
¥ 3,500.00
现货

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Background

GSK J4 is a potent cell-permeable inhibitor of the histone H3 lysine 27 (H3K27) demethylase JMJD3, an essential component of regulatory transcriptional chromatin complexes, with the half maximal inhibition concentration IC50 value > 50 μM in vitro [1].

GSK J4 is an ethyl ester derivative of GSK J1, which is a potent JMJD3 inhibitor (IC50: 60 nM) with restricted cellular permeability due to the highly polar carboxylate group, and rapidly hydrolyzed by macrophage esterase upon administration leading to the generation of pharmacologically relevant intracellular concentration of GSK-J1 [1].

GSK J4 has also been found to dose-dependently inhibit the production of tumor-necrosis factor-α (TNF-α), a LPS-driven cytokine involved in various fnflammatory disorders, with IC50 value of 9μM [1].

Reference

References:
[1] Kruidenier L, Chung CW, Cheng Z, Liddle J, Che K, Joberty G, Bantscheff M, Bountra C, Bridges A, Diallo H, Eberhard D, Hutchinson S, Jones E, Katso R, Leveridge M, Mander PK, Mosley J, Ramirez-Molina C, Rowland P, Schofield CJ, Sheppard RJ, Smith JE, Swales C, Tanner R, Thomas P, Tumber A, Drewes G, Oppermann U, Patel DJ, Lee K, Wilson DM. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature. 2012 Aug 16;488(7411):404-8. doi: 10.1038/nature11262.

文献引用

1. Li N, Yang L, et al. "BET bromodomain inhibitor JQ1 preferentially suppresses EBV-positive nasopharyngeal carcinoma cells partially through repressing c-Myc." Cell Death Dis. 2018 Jul 9;9(7):761. PMID:29988031

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt453.96
Cas No.1373423-53-0(free base)
FormulaC24H27N5O2.HCl
Solubility≥13.9 mg/mL in DMSO, <2.53 mg/mL in EtOH, <2.4 mg/mL in H2O
Chemical Nameethyl 3-[[2-pyridin-2-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]amino]propanoate
SDFDownload SDF
Canonical SMILESCCOC(=O)CCNC1=NC(=NC(=C1)N2CCC3=CC=CC=C3CC2)C4=CC=CC=N4.Cl
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

人类原代巨噬细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

1、3、10和31 μM;6小时

实验结果

GSK J4呈剂量依赖性地抑制TNF-α蛋白产生,其IC50值为9 μM。

动物实验 [2]:

动物模型

携带SF8628 K27M异种移植瘤的小鼠模型

给药剂量

100 mg/kg/day;腹腔注射;持续10天

实验结果

GSK J4显著抑制SF8628皮下肿瘤生长。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Kruidenier L, Chung CW, Cheng Z, Liddle J, Che K, Joberty G, Bantscheff M, Bountra C, Bridges A, Diallo H, Eberhard D, Hutchinson S, Jones E, Katso R, Leveridge M, Mander PK, Mosley J, Ramirez-Molina C, Rowland P, Schofield CJ, Sheppard RJ, Smith JE, Swales C, Tanner R, Thomas P, Tumber A, Drewes G, Oppermann U, Patel DJ, Lee K, Wilson DM. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature. 2012 Aug 16;488(7411):404-8.

[2]. Hashizume R, Andor N, Ihara Y, Lerner R, Gan H, Chen X, Fang D, Huang X, Tom MW, Ngo V, Solomon D, Mueller S, Paris PL, Zhang Z, Petritsch C, Gupta N, Waldman TA, James CD. Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nat Med. 2014 Dec;20(12):1394-6.

生物活性

描述 GSK J4 HCl是GSK-J1的乙酯衍生物。
靶点 JMJD3          
IC50            

质量控制

化学结构

GSK J4 HCl

相关生物数据

GSK J4 HCl