GSK J4 hydrochloride

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

GSK J4 HCl 是 GSK J1 的细胞渗透性前药，是 H3K27 组蛋白去甲基酶 JMJD3 和 UTX 的第一个选择性抑制剂，IC50 为 60 nM。

GSK J4 HCl is a cell permeable prodrug of GSK J1, which is the first selective inhibitor of the H3K27 histone demethylase JMJD3 and UTX with IC50 of 60 nM in a cell-free assay and inactive against a panel of demethylases of the JMJ family.(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).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.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.GSK-J4 inhibits JMJD3 expression that is induced by TGF-β1.GSK-J4 inhibits H3K4 demethylation at Xist, Nodal, and HoxC13 in female embryonic stem cells.(In Vivo):GSK-J4 Hydrochloride (10 mg/kg; i.p.; thrice-weekly for 10 weeks) attenuates the development of kidney disease in diabetic mice.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.

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).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. 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.GSK-J4 inhibits JMJD3 expression that is induced by TGF-β1.GSK-J4 inhibits H3K4 demethylation at Xist, Nodal, and HoxC13 in female embryonic stem cells.

GSK-J4 Hydrochloride (10 mg/kg; i.p.; thrice-weekly for 10 weeks) attenuates the development of kidney disease in diabetic mice.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. Animal Model:Eight-week-old male db/m and db/db mice 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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Chromatin/Epigenetic

Histone Demethylase

JMJD3

Inflammation/Immunology

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1373423-53-0

453.96

C24H27N5O2·HCl

>98% (HPLC)

Ethanol: 90 mg/mL warmed (198.25 mM); DMSO: 90 mg/mL warmed (198.25 mM)

CCOC(=O)CCNC1=NC(=NC(=C1)N1CCC2=CC=CC=C2CC1)C1=CC=CC=N1

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(-20℃)

With Ice Pack

≥ 2 years