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GSK J4 HCl
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
GSK J4 HCl图片
包装与价格:
包装价格(元)
10mM (in 1mL DMSO)电议
10mg电议
50mg电议

产品介绍
GSK J4 HCl 是 H3K27me3/me2-去甲基化酶 JMJD3/KDM6B 和 UTX/KDM6A 的有效双重抑制剂,IC50 分别为 8.6 和 6.6 μM。 GSK J4 HCl 抑制 LPS 诱导的 TNF-α;在人原代巨噬细胞中产生,IC50 为 9 μM. GSK J4 HCl 是 GSK-J1 的细胞渗透性前药。

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 ℃ 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 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.

产品描述

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.