PSI-7977

Cell lines

Non-infected Huh7.5.1 cells and JFH-1-infected Huh7.5.1 cells

Preparation method

The solubility of this compound in DMSO is >183mg/mL. 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

24 hours

Applications

PSI-7977 prevented PKR activation/ phosphory-lation in infected cells (5-6-fold decrease) and had no effect on the expression of inactive/non-phosphorylated PKR. It had no effect on the IFN-induced expression of non-phosphorylated and phosphorylated STAT1.

Animal models

TK-NOG mice with non-humanized (control) or humanized livers

Dosage form

Oral administration, 44 or 440 mg/kg/d, for 14 days

Applications

The average plasma ALT levels in mice with humanized livers in the 440- and 44-mg/kg/d treatment groups were below the upper limit of normal, and were not significantly different from those measured in vehicle-treated mice with humanized livers. The plasma lactate levels were also not elevated in or control mice or mice with humanized livers receiving either dose of PSI-7977.

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] Bobardt M, Chatterji U, Lim P, et al. Both Cyclophilin Inhibitors and Direct-Acting Antivirals Prevent PKR Activation in HCV-Infected Cells. The open virology journal, 2014, 8: 1.

[2] Xu D, Nishimura T, Nishimura S, et al. Fialuridine Induces Acute Liver Failure in Chimeric TK-NOG Mice: A Model for Detecting Hepatic Drug Toxicity Prior to Human Testing. PLoS medicine, 2014, 11(4): e1001628.