420205

GSK-J4

Histone Lysine Demethylase Inhibitor VIII, GSK-J4, CAS 1373423-53-0, is converted to GSK-J1 intracellularly for effective JMJD3 and UTX inhibition (~ 25 to 50 µM in HeLa cultures).

• Synonym(s): Histone Lysine Demethylase Inhibitor VIII, GSK-J4, GSK-J1 Pro-Drug, JHDM Inhibitor II Pro-Drug, Ethyl-3-(6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-ylamino)propanoate
• Empirical Formula (Hill Notation): C₂₄H₂₇N₅O₂
• CAS Number: 1373423-53-0
• Molecular Weight: 417.50
• UNSPSC Code: 12352200
• NACRES: NA.77
• MDL number: MFCD22683852
• Assay: ≥98% (HPLC)
• Form: semisolid
• Storage condition: OK to freeze, protect from light

Properties

• Product Name: Histone Lysine Demethylase Inhibitor VIII, GSK-J4, Histone Lysine Demethylase Inhibitor VIII, GSK-J4, CAS 1373423-53-0, is converted to GSK-J1 intracellularly for effective JMJD3 and UTX inhibition (~ 25 to 50 µM in HeLa cultures).
• Quality Segment: 100
• assay: ≥98% (HPLC)
• form: semisolid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze, protect from light
• color: tan
• solubility: DMSO: 100 mg/mL
• shipped in: ambient
• storage temp.: 2-8°C
• SMILES string: N3(CCc4c(cccc4)CC3)c1nc(nc(c1)NCCC(=O)OCC)c2ncccc2
• InChI: 1S/C24H27N5O2/c1-2-31-23(30)10-14-26-21-17-22(28-24(27-21)20-9-5-6-13-25-20)29-15-11-18-7-3-4-8-19(18)12-16-29/h3-9,13,17H,2,10-12,14-16H2,1H3,(H,26,27,28)
• InChI key: WBKCKEHGXNWYMO-UHFFFAOYSA-N

Description

General description

A cell-permeable GSK-J1 prodrug that is ineffective in cell-free assays, but is effectively converted to GSK-J1 intracellularly for effective JMJD3 and UTX inhibition (effective conc. 25 to 50 µM in HeLa cultures). GSK-J4 treatment is shown to block LPS-induced TNF-α production in primary human macrophage cultures (IC₅₀ = 9 µM by ELISA).
This probe is supplied in conjunction with the Structural Genomics Consortium (SGC). For further characterization details, please visit the SGC website (http://www.thesgc.org/scientists/chemical_probes/GSKJ1).

The H3K27me3 demethylase inhibitor GSK-J1 against JMJD3 and UTX is made cell-permeable by ethyl ester derivatization to facilitate cellular delivery ([medium GSK-J4]_t=0 = 30 µM; [cellular GSK-J1]_t=1h = 1.6 µM). The pro-drug GSK-J4, being ineffective in cell-free assays, is effectively converted to GSK-J1 intracellularly and inhibits nuclear H3K27me3 levels in both untransfected and JMJD3-transfected HeLa cells (25 to 50 µM). Simultaneous inhibition of cellular JMJD3 and UTX by GSK-J4 treatment is shown to block LPS-induced production of several proinflammatory cytokines, including TNF-α (IC₅₀ = 9 µM by ELISA), in primary human macrophage cultures.

Biochem/physiol Actions

Cell permeable: yes

Reversible: yes

Packaging

Packaged under inert gas

Preparation Note

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months for -20°C.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Disclaimer

Toxicity: Standard Handling (A)

Safety Information

• Storage Class: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point (°F): Not applicable
• Flash Point (°C): Not applicable