GSK J4 HCl
GSK J4 is a potent cell-permeable inhibitor of the histone H3 lysine 27 (H3K27) demethylase JMJD3, an essential component of regulatory transcriptional chromatin complexes, with the half maximal inhibition concentration IC50 value > 50 μM in vitro [1].
GSK J4 is an ethyl ester derivative of GSK J1, which is a potent JMJD3 inhibitor (IC50: 60 nM) with restricted cellular permeability due to the highly polar carboxylate group, and rapidly hydrolyzed by macrophage esterase upon administration leading to the generation of pharmacologically relevant intracellular concentration of GSK-J1 [1].
GSK J4 has also been found to dose-dependently inhibit the production of tumor-necrosis factor-α (TNF-α), a LPS-driven cytokine involved in various fnflammatory disorders, with IC50 value of 9μM [1].
Reference
References:
[1] Kruidenier L, Chung CW, Cheng Z, Liddle J, Che K, Joberty G, Bantscheff M, Bountra C, Bridges A, Diallo H, Eberhard D, Hutchinson S, Jones E, Katso R, Leveridge M, Mander PK, Mosley J, Ramirez-Molina C, Rowland P, Schofield CJ, Sheppard RJ, Smith JE, Swales C, Tanner R, Thomas P, Tumber A, Drewes G, Oppermann U, Patel DJ, Lee K, Wilson DM. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature. 2012 Aug 16;488(7411):404-8. doi: 10.1038/nature11262.
- 1. Silasi M, You Y, et al. "Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua." Sci Rep. 2020;10(1):5785. PMID:32238853
- 2. Li N, Yang L, et al. "BET bromodomain inhibitor JQ1 preferentially suppresses EBV-positive nasopharyngeal carcinoma cells partially through repressing c-Myc." Cell Death Dis. 2018 Jul 9;9(7):761. PMID:29988031
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 453.96 |
| Cas No. | 1797983-09-5 |
| Formula | C24H27N5O2·HCl |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥13.9 mg/mL in DMSO |
| Chemical Name | ethyl 3-[[2-pyridin-2-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]amino]propanoate |
| SDF | Download SDF |
| Canonical SMILES | CCOC(=O)CCNC1=NC(=NC(=C1)N2CCC3=CC=CC=C3CC2)C4=CC=CC=N4.Cl |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
|
Cell lines |
Human primary macrophages |
|
Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months. |
|
Reaction Conditions |
1, 3, 10 and 31 μM; 6 hrs |
|
Applications |
GSK J4 inhibited TNF-α protein production in a dose-dependent manner, with an IC50 value of 9 μM. |
| Animal experiment [2]: | |
|
Animal models |
Mice harboring subcutaneous SF8628 K27M xenografts |
|
Dosage form |
100 mg/kg/day; i.p.; for 10 days |
|
Applications |
GSK J4 showed significant growth-inhibitory activity against SF8628 subcutaneous tumors. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1]. Kruidenier L, Chung CW, Cheng Z, Liddle J, Che K, Joberty G, Bantscheff M, Bountra C, Bridges A, Diallo H, Eberhard D, Hutchinson S, Jones E, Katso R, Leveridge M, Mander PK, Mosley J, Ramirez-Molina C, Rowland P, Schofield CJ, Sheppard RJ, Smith JE, Swales C, Tanner R, Thomas P, Tumber A, Drewes G, Oppermann U, Patel DJ, Lee K, Wilson DM. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature. 2012 Aug 16;488(7411):404-8. [2]. Hashizume R, Andor N, Ihara Y, Lerner R, Gan H, Chen X, Fang D, Huang X, Tom MW, Ngo V, Solomon D, Mueller S, Paris PL, Zhang Z, Petritsch C, Gupta N, Waldman TA, James CD. Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nat Med. 2014 Dec;20(12):1394-6. |
|
| Description | GSK J4 HCl is an ethyl ester derivative of GSK-J1. | |||||
| Targets | JMJD3 | |||||
| IC50 | ||||||
Quality Control & MSDS
- View current batch:
Chemical structure
Related Biological Data
Related Biological Data
Related Biological Data
