GSK2606414 is a cell-permeable and orally active protein kinase R-like endoplasmic reticulum kinase(PERK)inhibitor with IC50 of 0.4 nM. GSK2606414 inhibits PERK activation in cells and suppresses the growth of human tumor xenografts in mice.

N2A cells:5.3 μM, EIF2AK1 (HRI):420 nM, EIF2AK2 (PKR):696 nM, ARPE-19 cells:1.7 µM, KIT (tyrosine kinase receptor):154 nM, EIF2AK3 (PERK):0.4 nM

METHODS: S1-M1-80 vector and S1-M1-80 sgABCG2 cells were treated with GSK2606414 (0.1, 1, 3, 10, 30, 100 μM, 72 hours), and cytotoxicity was determined by MTT assay.
RESULTS GSK2606414 showed dose-dependent cytotoxic effects on both cell lines. [2]
METHODS: N2A cells were treated with GSK2606414 (0.5, 1 μM, 24 hours) and high glucose (30 mM), cells were lysed, and Western blot analysis was performed.
RESULTS N2A cells treated with GSK2606414 reduced the phosphorylation of eIF2α in cells and significantly reduced p-PERK levels in a dose-dependent manner, and GSK2606414 could inhibit the PERK/p-eIF2α/ATF4/CHOP signaling axis. [3]

METHODS: GSK2606414 (50, 150 mg/kg, oral, twice a day, 21 days) was used to treat mice bearing subcutaneous pancreatic human BxPC3 tumors and the effect on tumor growth was observed.
RESULTS GSK2606414 inhibited tumor growth in a dose-dependent manner, with the tumor growth inhibition rates of 20% and 59% at the two doses, respectively. [1]