The histone H3 lysine 27 (H3K27) demethylase JMJD3 plays important roles in the transcriptional regulation of cell differentiation, development, the inflammatory response, and cancer.[1],[2]. GSK-J4 is a cell-permeable prodrug which is modified by intracellular esterases to give GSK-J1, an inhibitor of JMJD3. GSK-J5 is a pyridine regio-isomer of GSK-J4. Like GSK-J4, this isomer is cell-permeable and hydrolyzed to a free base.3 However, the free base is a weak inhibitor of JMJD3 (IC50 > 100 μM), making it an ideal inactive control molecule for elucidating the functional role of JMJD3 inhibition.[3]
Reference:
[1]. Agger, K., Cloos, P.A.C., Christensen, J., et al. UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nat.Lett. 449(7163), 731-734 (2011).
[2]. Hübner, M.R., and Spector, D.L. Role of H3K27 demethylases Jmjd3 and UTX in transcriptional regulation. Cold Spring Harb.Symp.Quant.Biol. 75, 43-49 (2010).
[3]. Kruidenier, L., Chung, C.W., Cheng, Z., et al. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature 488, 404-408 (2012).