Biological Activity
GSK-J4 is a potent H3K27me3 histone lysine demethylase (KDM) inhibitor, with IC50s of 8.6 μM and 6.6 μM against KDM6B and KDM6A, respectively.
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 (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[2]. GSK-J4 inhibits the KDM6 family of H3K27me3 demethylases JMJD3 and UTX. GSK-J4 inhibits JMJD3 expression that is induced by TGF-β1[3]. GSK-J4 inhibits H3K4 demethylation at Xist, Nodal, and HoxC13 in female embryonic stem cells[4].
In Vivo
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[2].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.