GSK J4 HCl

GSK-J4 (1373423-53-0) is a histone demethylase JMJD3/UTX inhibitor. Inhibits demethylation of histone H3K27. Reduces LPS-induced proinflammatory cytokine production in primary human macrophages (IC50 = 9 μM for the inhibition of TNFα release). Cell permeable, ethyl ester of GSK J1 (cat.# 10-1393).1 GSK-J4 rescues newborn pups from embryonic lethality in BRAF knockin mice which recapitulate major features of RASopathies.2

GSK-J4 has been used to study the effect of KDM2B (Jumonji (JmjC) domain histone 3 lysine 36 (H3K36) di-demethylase) inhibition on the survival and DNA repair potential of glioblastoma cells. It has also been used in sulforhodamine B (SRB) cell growth assay and cell viability assay.

ChEBI: 3-[[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-4-pyrimidinyl]amino]propanoic acid ethyl ester is an organonitrogen heterocyclic compound.

GSK-J4 is cell permeable prodrug rapidly hydrolysed by macrophage esterases to GSK-J1, a potent selective jumonji H3K27 demethylase inhibitor. 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. For characterization details for GSK-J4 and full characterization details for GSK-J1, please visit the GSK-J1 probe summary on the Structural Genomics Consortium (SGC) website.To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc

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1) Kruidenier et al. (2012), Selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response; Nature, 488 404 2) Inoue et al. (2014) New Braf knockin mice provide a pathogenic mechanism of developmental defects and therapeutic approach in cardio-facio-cutaneous syndrome; Hum. Mol. Genet.,?23?6553