1373423-53-0
基本信息
H3K27ME3DEMETHYLASE抑制剂(GSK-J4)
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
GSK J4
CS-1667
CS-2143
GSK J4 HCl
GSK J4 free base
GSKJ4HCL(free base)
GSK J4 HCl USP/EP/BP
H3K27 histone demethylase inhibitor J4 HCl
Histone Lysine Demethylase Inhibitor VIII, GSK-J4
物理化学性质
| 沸点 | 581.2±50.0 °C(Predicted) |
| 密度 | 1.216±0.06 g/cm3(Predicted) |
| 储存条件 | 2-8°C |
| 溶解度 | 在DMSO中的溶解度为20mg/mL，澄清 |
| 酸度系数(pKa) | 5.95±0.10(Predicted) |
| 形态 | 棕褐色半固体状 |
| 颜色 | 白色至米色 |
| 稳定性 | 可在-20°下的DMSO或乙醇溶液保存长达3个月。 |
| InChIKey | WBKCKEHGXNWYMO-UHFFFAOYSA-N |
安全数据
| 危险性符号(GHS) |  GHS07 |
| 警示词 | 警告 |
| 危险性描述 | H319-H315-H335 |
| 防范说明 | P264-P280-P302+P352-P321-P332+P313-P362-P264-P280-P305+P351+P338-P337+P313P |
| 危险品标志 | Xi |
| 危险类别码 | 36/37/38 |
| 安全说明 | 26 |
| WGK Germany | 3 |
常见问题列表
IC50: 8.6 µM (JMJD3/KDM6B), 6.6 µM (UTX/KDM6A)
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. |