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- CAS Registry #:1373423-53-0
- Formula:C24H27N5O2 • HCl
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| Description: |
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 and inactive against a panel of demethylases of the JMJ family. |
| Background: |
GSK J4 is a potent cell-permeable inhibitor of the histone H3 lysine 27 (H3K27) demethylase JMJD3. GSK J4 is an ethyl ester derivative of GSK J1, a 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 . GSK J4 has been found to dose-dependently inhibit the production of tumor-necrosis factor-α (TNF-α), a LPS-driven cytokine involved in various fnflammatory disorders (IC50 = 9 µM). |
| Synonym(s): |
ethyl 3-[[2-pyridin-2-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]amino]propanoate |
| Purity: |
≥98% by HPLC |
| Biological Activity: |
Inhibits JMJD3 and UTX with IC50 of 60 nM and inactive against a panel of demethylases of the JMJ family (IC50 value > 50 µM). |
| Solubility: |
Soluble in DMSO 84 mg/ml, water 84 mg/ml, ethanol 84 mg/ml |
| Storage / Stability: |
Store at or below –20°C. Solid form is stable at least 12 months from date of receipt, when stored as directed. Do not store aqueous solutions for more than one day. |
| Reference(s): |
Kruidenier L, et al. Nature. 2012 Aug 16;488(7411):404-8. |
| Scientific Category: |
Demethylase(s) |
| Product Type: |
Inhibitors / Activators |
