Biological Activity
GSK2656157 is a selective and ATP-competitive inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) with an IC50 of 0.9 nM.
In Vitro
GSK2656157 results in inhibition of PERK activation as well as decreases in the downstream substrates, phospho-eIF2α, ATF4, and CHOP with an IC50 in the range of 10-30 nM in the BxPC3 pancreatic tumor cell line. Cells that are exposed to 1 μM GSK2656157 before UPR induction are able to block this effect on de novo protein synthesis[1]. GSK2656157 causes the activation of another eIF2α kinase to compensate for the loss of PERK activity in HT1080 cells. GSK2656157 inhibits the growth of the HT1080 cells[2]. GSK2656157 inhibits LPS-induced IL-1β production, LPS-induced Caspase 1 activation and LPS-induced eIF-2α phosphorylation, but does not inhibit LPS-induced TNF-α production[3].
In Vivo
GSK2656157 (1.5-150 mg/kg, p.o.) results in dose-dependent inhibition of phospho-PERK Thr980, with more than 80% inhibition at 50 and 150 mg/kg. GSK2656157 (50-150 mg/kg, p.o.) results in dose-dependent inhibition of tumor growth in human tumor xenograft models[1].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.