Description
The histone H3 lysine 27 (H3K27) demethylase JMJD3 plays important roles in the transcriptional regulation of cell differentiation, development, the inflammatory response, and cancer. GSK-
J4 (hydrochloride) is an ethyl ester derivative of the JMJD3 selective histone demethylase inhibitor GSK-
J1 with an IC
50 value greater than 50 μM
in vitro. Acting as a prodrug, GSK-
J4 is rapidly hydrolyzed in cells to the otherwise cell impermeable GSK-
J1, which exhibits an IC
50 value of 60 nM for the purified enzyme. When administered to human primary macrophages, GSK-
J4 can reduce LPS-
induced proinflammatory cytokine production, most notably including that of TNFα (IC
50 = 9 μM).
References
[1] KARL AGGER. UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development[J]. Nature, 2007, 449 7163: 731-734. DOI:
10.1038/nature06145[2] M R HüBNER D L S. Role of H3K27 demethylases Jmjd3 and UTX in transcriptional regulation.[J]. Cold Spring Harbor symposia on quantitative biology, 2010: 43-49. DOI:
10.1101/sqb.2010.75.020[3] LAURENS KRUIDENIER. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response[J]. Nature, 2012, 488 7411: 404-408. DOI:
10.1038/nature11262[4] BO YANG. Reepithelialization of Diabetic Skin and Mucosal Wounds Is Rescued by Treatment With Epigenetic Inhibitors.[J]. Diabetes, 2024: 120-134. DOI:
10.2337/db23-0258
