GSK2656157

Cell lines

HT1080 cells

Preparation method

The solubility of this compound in DMSO is > 20.8 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

0.1-10 µM, 24 h

Applications

In HT1080 cells, 0.1 μM GSK2656157 was efficient to block the activity of PERK. Cells treated with GSK2656157 exhibited increasing eIF2α phosphorylation in order to compensating the loss of PERK.

Animal models

Eight- to twelve-week-old naive female CD-1, female nu/nu CD-1 mice and severe combined immunodeficient (SCID) mice

Dosage form

50, 150 mg/kg, twice daily

Application

After a single 50 mg/kg oral dose of GSK2656157, mice occurs inhibited phospho-PERK in the pancreas completely through 8 hours. And the activity of PERK was recovered to almost normal levels at 18 hours. Twice daily administration of 50 or 150 mg/kg GSK2656157 to mice resulted in an inhibition of multiple tumor xenografts growth in a dose-dependent manner.

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]. Krishnamoorthy J, Rajesh K, Mirzajani F, et al. Evidence for eIF2α phosphorylation-independent effects of GSK2656157, a novel catalytic inhibitor of PERK with clinical implications[J]. Cell Cycle, 2014, 13(5): 801-806.

[2]. Atkins C, Liu Q, Minthorn E, et al. Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity[J]. Cancer research, 2013, 73(6): 1993-2002.