Home>>Signaling Pathways>> Chromatin/Epigenetics>> Histone Demethylases>>GSK J4 HCl

GSK J4 HCl

Catalog No.GC15497

Prodrug of a selective H3K27 histone demethylase inhibitor

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GSK J4 HCl Chemical Structure

Cas No.: 1797983-09-5

Size Price Stock Qty
10mM (in 1mL DMSO)
$92.00
In stock
10mg
$85.00
In stock
50mg
$271.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

Human foreskin fibroblasts (HFFs, ATCC SCRC-1041) cells

Preparation Method

The T. gondii tachyzoites were maintained by repeat passage in monolayers of HFFs grown in DMEM supplemented with 10% (v/v) FBS and a cocktail of 1% (v/v) penicillin-streptomycin -glutamine at 37 °C and 5% CO2 .

Reaction Conditions

GSK J4 HCl with initial concentration of 100 μM in the culture medium was added to the first column of HFFs (~ 250 cells/well) in a 96-well half-area plate and then diluted serially across the plate by 2-fold dilutions, leaving the final column drug-free. Fifty tachyzoites were then added at a MOI of 1:5 to each well in six of the eight rows. After a 72h incubation, CPRG was added, and the absorbance was measured at 570 nm. Moreover, to measure the effect of each compound on the viability of host cells, CCK8 reagent was added to the two rows of uninfected HFFs and absorbance at 450 nm was measured after 2 h.

Applications

GSK-J4 HCl could inhibit T. gondii and show ability against toxoplasmosis.

Animal experiment [1]:

Animal models

Female BALB/c mice (6–8 weeks old, ~20 g)

Preparation Method

Mice were divided into 4 groups consisting of 15 mice each and injected intraperitoneally with 103 RH strains per animal. GSK J4 HCl were dissolved in DMSO and diluted in PBS prior to feeding to mice. After 4 h of infection, mice were orally administered with GSK J4 HCl for 5 consecutive days and were monitored for 30 days. Mice treated with pyrimethamine (50 mg/kg) were used as a positive control, and 1 ml PBS containing 11 μl of DMSO was used as a negative control.

Dosage form

50 mg/kg

Applications

GSK J4 HCl could significantly elongate the survival time in acute murine toxoplasmosis model. GSK-J4 HCl is a promising candidate for the treatment and prevention of toxoplasmosis.

References:

[1]. Liu S, et al. Two old drugs, NVP-AEW541 and GSK-J4, repurposed against the Toxoplasma gondii RH strain. Parasit Vectors. 2020 May 11;13(1):242.

Background

GSK-J4 HCl is a small-molecule inhibitor with highly efficient cell permeability and a pharmacologically selective inhibitor that preserves H3K27 methylation by inhibiting KDM6B. GSK-J4 HCl acts by interacting with α-ketoglutarate binding at the catalytic site of KDM6B. In addition, treatment with GSK-J4 HCl induced cell cycle arrest and cell death in different kinds of cancer cells with dismal toxicity to normal cells.

In vitro experiment indicated that GSK-J4 HCl could inhibit T. gondii at IC50 values of 2.37 μM. In addition, the TD50 value of GSK-J4 HCl against HFF was 34.6 μM. Based on these results, the calculated in vitro TI was 14.6 for GSK-J4 HCl. These data suggest that GSK-J4 HCl is a potent drug candidate against toxoplasmosis. In vivo study indicated that GSK J4 HCl could significantly elongate the survival time in acute murine toxoplasmosis model. Moreover, GSK-J4 HCl is a promising candidate for the treatment and prevention of toxoplasmosis.[1]

References:
[1].Liu S, et al. Two old drugs, NVP-AEW541 and GSK-J4, repurposed against the Toxoplasma gondii RH strain. Parasit Vectors. 2020 May 11;13(1):242.

Chemical Properties

Cas No. 1797983-09-5 SDF
Chemical Name ethyl 3-[[2-pyridin-2-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]amino]propanoate
Canonical SMILES CCOC(=O)CCNC1=NC(=NC(=C1)N2CCC3=CC=CC=C3CC2)C4=CC=CC=N4.Cl
Formula C24H27N5O2.HCl M.Wt 453.96
Solubility ≥ 13.9 mg/mL in DMSO, <2.53 mg/mL in EtOH, <2.4 mg/mL in Water Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.2028 mL 11.0142 mL 22.0284 mL
5 mM 0.4406 mL 2.2028 mL 4.4057 mL
10 mM 0.2203 mL 1.1014 mL 2.2028 mL
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