GSK-J1

Description: GSKJ1 (GSK-J1; GSK-J 1; GSK-J-1) is a novel, highly selective and potent inhibitor of histone demethylase (H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A) with potential antineoplastic activity. It that has significant activity (IC50 60 nM for human JmjD3) in vitro and in cell assays using an ester prodrug derivative (GSK-J4: 1 uM < IC50 < 10 uM; e.g. 9 uM in primary human macrophages). The KDM5/JARID1 family of Fe(II)- and alpha-ketoglutarate-dependent demethylases remove methyl groups from tri- and dimethylated lysine 4 of histone H3. Accumulating evidence from primary tumors and model systems supports a role for KDM5A (JARID1A/RBP2) and KDM5B (JARID1B/PLU1) as oncogenic drivers. The pyridine regio-isomer GSK-J2 displays significantly less on-target activity (IC50 > 100 uM for human JmjD3) and thus can be used as control for target effects in vitro, and as ester derivative (GSK-J5) in cells. Recent data has shown that GSK-J1 also shows some activity (IC50 950 nM for Jarid1b, IC50 1.76 uM for Jarid1c) against H3K4me3/2/1 demethylases.

References: Nature. 2012 Aug 16; 488(7411):404-8; J Cell Biochem. 2015 Nov; 116(11):2628-36

Related CAS#:1394854-52-4 (GSK-J2); 1797983-09-5 (GSK J4 HCl, prodrug of GSK J1); 1373423-53-0(GSK J4, prodrug of GSK J1); 1797832-71-3 (GSKJ1 sodium)