product name GSK-J4
Description: GSK J4 is a novel, cell permeable, and potent 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. GSK-J4 is used to probe the consequences of demethylation of H3K27me3. GSK-J4 inhibits the lipopolysaccharide-induced production of cytokines, including pro-inflammatory tumour necrosis factor (TNF).
References: Nature. 2012 Aug 16;488(7411):404-8.
417.5
Formula
C24H27N5O2
CAS No.
1373423-53-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: ≥ 36 mg/mL
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19428191
| In Vitro |
In vitro activity: GSK J4 HCl is an ethyl ester derivative of the JMJD3 selective histone demethylase inhibitor GSK-J1 with an IC50 value greater than 50 μM in vitro. GSK J4 HCl is used to probe the consequences of demethylation of H3K27me3. In human primary macrophages, GSK-J4 inhibits the lipopolysaccharide-induced production of cytokines, including pro-inflammatory tumour necrosis factor (TNF). In addition, GSK-J4 prevents the lipopolysaccharide-induced loss of H3K27me3 associated with the TNF transcription start sites and blocked the recruitment of RNA polymerase II. Kinase Assay: Jumonji C domain-containing histone demethylases (JHDMs) are Fe(II) and α-ketoglutarate dependent enzymes that oxygenate methylated histone lysine residues and thereby cause their demethylation. GSK-J1 is selective for the KDM6 subfamily members JMJD3 and UTX with an IC50 of 60 nM in a JMJD3 assay, and is inactive against other demethylases of the JMJ family and over 100 tested kinases and histone deacetylases. The prodrug GSK-J4 inhibited TNF-α production with an IC50 of 9 μM in LPS-stimulated human macrophages and blocked the production of TNF-α by macrophages derived from patients with rheumatoid arthritis. GSK J4 is an inhibitor of JMJD3 and UTX. Cell Assay: GSK J4 inhibited TNF-α protein production in a dose-dependent manner, with an IC50 value of 9 μM. Cells used: Human primary macrophages |
|---|---|
| In Vivo | GSK J4 showed significant growth-inhibitory activity against SF8628 subcutaneous tumors. |
| Animal model | Mice harboring subcutaneous SF8628 K27M xenografts |
| Formulation & Dosage | 100 mg/kg/day; i.p.; for 10 days |
| References | Nature. 2012 Aug 16;488(7411):404-8; Nat Med. 2014 Dec;20(12):1394-6. |
