GSK-J4 是一种有效的 H3K27me3/me2 去甲基化酶JMJD3/KDM6B和UTX/KDM6A双抑制剂,IC50分别为 8.6 μM 和 6.6 μM。GSK-J4 抑制 LPS 诱导的人原代巨噬细胞产生 TNF-α,IC50值为 9 μM。GSK-J4 是 GSK-J1 的细胞通透性前药。GSK-J4 诱导内质网应激相关的细胞凋亡 (apoptosis)。
生物活性 | GSK-J4 is a potent dual inhibitor of H3K27me3/me2-demethylasesJMJD3/KDM6BandUTX/KDM6AwithIC50s of 8.6 and 6.6 μM, respectively. GSK-J4 inhibits LPS-induced TNF-α production in human primary macrophages with an IC50of 9 μM. GSK J4 is a cell permeable prodrug of GSK-J1[1][2][3]. GSK-J4 induces endoplasmic reticulum stress-relatedapoptosis[4]. |
IC50& Target | IC50: 8.6 μM (JMJD3/KDM6B), 6.6 μM (UTX/KDM6A)[6] |
体外研究 (In Vitro) | 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 atXist,Nodal, andHoxC13in female embryonic stem cells[5].
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体内研究 (In Vivo) | 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].
Animal Model: | Eight-week-old male db/m and db/db mice[2] | Dosage: | 10 mg/kg | Administration: | i.p.; thrice-weekly for 10 weeks | Result: | Attenuated the development of kidney disease in diabetic mice. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : ≥ 36 mg/mL(86.23 mM) *"≥" means soluble, but saturation unknown. 配制储备液 1 mM | 2.3952 mL | 11.9760 mL | 23.9521 mL | 5 mM | 0.4790 mL | 2.3952 mL | 4.7904 mL | 10 mM | 0.2395 mL | 1.1976 mL | 2.3952 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (4.98 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.98 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (4.98 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.98 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (4.98 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.98 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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