1373423-53-0 Usage
Description
GSK J4 HCl, also known as GSK-J4, is a histone demethylase JMJD3/UTX inhibitor that specifically inhibits the demethylation of histone H3K27. It is a cell-permeable, ethyl ester of GSK J1 and has been shown to reduce LPS-induced proinflammatory cytokine production in primary human macrophages. GSK J4 HCl has also demonstrated potential in rescuing newborn pups from embryonic lethality in BRAF knockin mice, which exhibit major features of RASopathies.
Uses
Used in Pharmaceutical Research:
GSK J4 HCl is used as a research compound for studying the effects of histone demethylase JMJD3/UTX inhibition on various cellular processes and diseases. It is particularly useful in understanding the role of histone demethylation in the regulation of gene expression and its implications in cancer and inflammatory responses.
Used in Glioblastoma Research:
GSK J4 HCl is used as a histone demethylase inhibitor for studying the effect of KDM2B inhibition on the survival and DNA repair potential of glioblastoma cells. This application helps researchers understand the role of histone demethylation in the development and progression of glioblastoma, a highly aggressive form of brain cancer.
Used in Cell Growth and Viability Assays:
GSK J4 HCl is used as a test compound in sulforhodamine B (SRB) cell growth assay and cell viability assay. These assays are essential for evaluating the effects of GSK J4 HCl on cell proliferation and survival, which can provide valuable insights into its potential therapeutic applications.
Used in Inflammatory Response Studies:
GSK J4 HCl is used as an inhibitor of histone demethylation to study its effects on LPS-induced proinflammatory cytokine production in primary human macrophages. This application helps researchers understand the role of histone demethylation in regulating inflammatory responses and its potential as a target for anti-inflammatory therapies.
Used in RASopathies Research:
GSK J4 HCl is used as a therapeutic agent for rescuing newborn pups from embryonic lethality in BRAF knockin mice, which recapitulate major features of RASopathies. This application aids in understanding the role of histone demethylation in the development of RASopathies and the potential of GSK J4 HCl as a therapeutic agent for these disorders.
Biochem/physiol Actions
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
References
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
Check Digit Verification of cas no
The CAS Registry Mumber 1373423-53-0 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,3,7,3,4,2 and 3 respectively; the second part has 2 digits, 5 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 1373423-53:
(9*1)+(8*3)+(7*7)+(6*3)+(5*4)+(4*2)+(3*3)+(2*5)+(1*3)=150
150 % 10 = 0
So 1373423-53-0 is a valid CAS Registry Number.
1373423-53-0Relevant articles and documents
Immobilization products and methods for the identification of histone demethylase interacting molecules and for the purification of histone demethylase proteins
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Page/Page column, (2013/05/23)
The present invention relates to immobilization products comprising compounds of formula (I) and preparations thereof as well as methods and uses for the identification of histone demethylase interacting compounds or for the purification or identification of histone demethylase proteins.
