GSK J4 HCl
(Synonyms: GSK-J4盐酸盐) 目录号 : GC15497
GSK-J4 HCl 是一种小分子抑制剂，具有高效的细胞渗透性和药理学选择性抑制剂，可通过抑制 KDM6B 来保持 H3K27 甲基化。
Cas No.:1797983-09-5
Sample solution is provided at 25 µL, 10mM.
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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.
GSK-J4 HCl 是一种小分子抑制剂,具有高效的细胞渗透性和药理学选择性抑制剂,可通过抑制 KDM6B 来保持 H3K27 甲基化。 GSK-J4 HCl 通过与 KDM6B 催化位点的 α-酮戊二酸结合相互作用发挥作用。此外,GSK-J4 HCl处理可诱导不同类型癌细胞的细胞周期停滞和细胞死亡,对正常细胞具有不良毒性。
体外实验表明,GSK-J4 HCl 可以抑制弓形虫,IC50 值为 2.37 μM。此外,GSK-J4 HCl 对 HFF 的 TD50 值为 34.6 μM。基于这些结果,计算出的 GSK-J4 HCl 体外 TI 为 14.6。这些数据表明 GSK-J4 HCl 是一种有效的抗弓形虫病候选药物。体内研究表明,GSK J4 HCl 可显着延长急性小鼠弓形虫病模型的存活时间。此外,GSK-J4 HCl 有望成为治疗和预防弓形虫病的候选药物。[1]
| 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) |
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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. |
|
| Cas No. | 1797983-09-5 | SDF | |
| 别名 | GSK-J4盐酸盐 | ||
| 化学名 | 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 | ||
| 分子式 | C24H27N5O2.HCl | 分子量 | 453.96 |
| 溶解度 | ≥ 13.9 mg/mL in DMSO, <2.53 mg/mL in EtOH, <2.4 mg/mL in Water | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet