GSK J4 HCl |
Catalog No.GC15497 |
Prodrug of a selective H3K27 histone demethylase inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1797983-09-5
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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. |
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.
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. |
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Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
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