GSK J4 HCl

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 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.