The Jumonji (JMJ) family of histone demethylases are Fe2+- and α-ketoglutarate-dependent oxygenases implicated in chromatin modifications. GSK-J1 is a selective inhibitor of Jumonji H3K27 demethylase. The IC50 value of GSK-J1 for JMJD3 is 60nM.[3] GSK-J1 inhibited the demethylase activity of KDM5C and KDM5B with IC50 values of ~11 and ~94μM, respectively.[4] Subretinal injection of P0 rats with GSK-J1 (1mM) enhanced the accumulation of cell cycle marker Ki67 and cell proliferation, and affected apoptosis and neuronal maturation in developing retina.[5]
作用机制
GSK-J1 is a Jumonji H3K27 demethylase inhibitor. It is competitive with α-ketoglutarate but non-competitive with the peptide substrate. The propanoic acid of GSK-J1 mimics α-ketoglutarate binding by interacting with K1381, T1387, and N1480.[3]
GSK-J1 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Mouse mammary epithelial cells (MECs)
0.1 µM, 1 µM, 10 µM
18 hours
To evaluate the cytotoxicity of GSK-J1 on mouse mammary epithelial cells, the results showed significant cytotoxicity at 100 μM, so 0.1 μM, 1 μM, and 10 μM were chosen for subsequent experiments.
J Biol Chem. 2022 Jun;298(6):102017.
Cal27 cells
20 µM
48 hours
GSK-J1 in combination with TCP significantly induced cell apoptosis and senescence, and inhibited cell proliferation.
Br J Cancer. 2020 Feb;122(4):528-538.
FaDu cells
15 µM
48 hours
GSK-J1 in combination with TCP significantly induced cell apoptosis and senescence, and inhibited cell proliferation.
Br J Cancer. 2020 Feb;122(4):528-538.
MCF7
20 µM
72 hours
To evaluate the effect of GSK-J1 on breast cancer cell growth, results showed that the growth inhibitory concentration of GSK-J4 on MCF7 cells was 0.9–1.0 μM.
J Biol Chem. 2016 Feb 5;291(6):2631-46.
MDA-MB231
20 µM
72 hours
To evaluate the effect of GSK-J1 on breast cancer cell growth, results showed that the growth inhibitory concentration of GSK-J4 on MDA-MB231 cells was 2.9 μM.
J Biol Chem. 2016 Feb 5;291(6):2631-46.
Mouse mammary epithelial cells (MECs)
0.1 µM, 1 µM, 10 µM
To evaluate the effect of GSK-J1 on the expression of inflammatory factors in LPS-stimulated mouse mammary epithelial cells, the results showed that GSK-J1 significantly reduced the expression of Tnfa, Il1b, and Il6.
J Biol Chem. 2022 Jun;298(6):102017.
GSK-J1 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rats
Sleep-wake cycle model
Intraperitoneal injection
0.1, 1.0, or 10 mg/kg
Single injection, lasting 4 hours
GSK-J1, when administered during the dark phase, reduced wakefulness, increased slow wave sleep and rapid eye movement sleep time, and decreased levels of sleep-related neurochemicals
Front Neurosci. 2019 Mar 15;13:237
BALB/c mice
LPS-induced mastitis model
Intraperitoneal injection
1 mg/kg
Single dose, lasting 24 hours
To evaluate the effect of GSK-J1 on the inflammatory response in the mammary tissue of LPS-induced mastitis model mice, the results showed that GSK-J1 significantly alleviated the inflammatory response in the mammary tissue, reducing inflammatory cell infiltration and the expression of inflammatory factors.
J Biol Chem. 2022 Jun;298(6):102017.
C57BL/6 mice
4NQO-induced HNSCC model and xenograft model
Intraperitoneal injection
25 mg/kg
5 days a week for 3 weeks
GSK-J1 in combination with TCP significantly inhibited tumor growth and progression, reducing tumor volume and weight.
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